Topical compositions containing rose oil and cannabidiol and methods of making and using the same

ABSTRACT

The present disclosure provides compositions of rose oil, cannabidiol, and humectants and methods of using said compositions. The present disclosure also products containing the aforementioned products, including a face mask, a serum, a lotion, and an eye cream.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional No. 62/944,613,filed Dec. 6, 2019, the content of which is incorporated by referenceherein in its entirety.

FIELD

The disclosure relates to compositions containing cannabidiol and roseoil. The resulting compositions can be used in skin care products, suchas lotions, serums, eye creams, or face masks. The disclosure furtherrelates to methods of applying such products.

BACKGROUND OF THE INVENTION

Aging, chronic exposure to adverse environmental factors, malnutrition,puberty, and fatigue can change the visual appearance, physicalproperties, or physiological functions of skin in ways that areconsidered visually undesirable. The most notable and obvious changesinclude the development of fine lines and wrinkles, loss of elasticity,increased sagging, loss of firmness, loss of color evenness or tone,coarse surface texture, and mottled pigmentation. Less obvious, butmeasurable changes which occur as skin ages or endures chronicenvironmental insult, include a general reduction in cellular and tissuevitality, reduction in cell replication rates, reduced cutaneous bloodflow, reduced moisture content, alterations in regulation of commonbiochemical pathways, and a reduction in the skin's ability to remodeland repair itself. Many of the alterations in appearance and function ofthe skin are caused by changes in the outer epidermal layer of the skin,while others are caused by changes in the lower dermis.

Many skin care compositions cause side effects, such as irritation,dermatitis, and acne. Therefore, there remains a need in the art in thecosmetics industry to develop skin care compositions, which positivelyaffect skin health.

SUMMARY OF THE INVENTION

Topical compositions containing rose oil and cannabidiol and methods ofmaking the same are described herein.

In some aspects, the present disclosure provides a topical skin carecomposition comprising: (i) rose oil; (ii) cannabidiol (CBD), and (iii)a humectant, wherein the composition is delivered to skin by a cosmeticvehicle.

In some embodiments, the topical skin care composition comprises up toabout 5 rose oil and up to about 2% CBD.

In some embodiments, the topical skin care composition comprises up toabout 2% of a humectant.

In some embodiments, the topical skin care composition comprises ahumectant selected from the group consisting of Aloe vera extract,glyceryl glucoside, and hyaluronic acid.

In some embodiments, the topical skin care composition comprises ahumectant, wherein the humectant is hyaluronic acid.

In some embodiments, the topical skin care composition comprises ahumectant, wherein the humectant is glyceryl glucoside.

In some embodiments, the topical skin care composition comprises roseoil, wherein the rose oil is an extract of Rhododendron ferrugineum.

In some embodiments, the topical skin care composition comprises roseoil, wherein the rose oil is an extract of Rhododendron ferrugineum, andwherein the extract comprises stem cells.

In some embodiments, the topical skin care composition comprises roseoil, wherein the rose oil is an extract of Rosa damascena.

In some embodiments, the topical skin care composition comprises acosmetic vehicle, wherein the cosmetic vehicle is selected from thegroup consisting of liposome, nanosome, oil-in-water emulsion, andwater-in-oil emulsion.

In some embodiments, the topical skin care composition comprises acosmetic vehicle, wherein the cosmetic vehicle is a nanosome.

In some embodiments, the topical skin care composition comprises acosmetic vehicle, wherein the cosmetic vehicle is a nanosome, whereinthe nanosome has an average particle size of 90 nm.

In some embodiments, the topical skin care composition comprises acosmetic vehicle, wherein the cosmetic vehicle is an oil-in-wateremulsion.

In some embodiments, the topical skin care composition comprises acosmetic vehicle, wherein the cosmetic vehicle comprises up to about 60%glycerin, up to about 15% caprylic/capric triglycerides, and up to about3% phospholipids.

In some embodiments, the topical skin care compositions of the presentinvention further comprise tocopherol.

In some aspects, the present disclosure provides a method of applying atopical skin care composition to skin, comprising topically applying thetopical skin care composition, wherein the topical skin compositioncomprises (i) rose oil; (ii) cannabidiol (CBD), and (iii) a humectant.

In some aspects, the present disclosure provides a method of applying atopical skin care composition to skin, wherein the composition isapplied to a face.

In some aspects, the present disclosure provides a method of applying atopical skin care composition to skin, wherein the composition isapplied to a wrinkle.

In some aspects, the present disclosure provides a method of applying atopical skin care composition to skin, wherein the composition isapplied to a fine line.

In some aspects, the present disclosure provides a method of reducingacne comprising applying the topical skin care composition comprising(i) rose oil; (ii) cannabidiol (CBD), and (iii) a humectant to the skin

In some embodiments, the present disclosure provides a kit comprising atopical skin composition of the present invention combined with adispensing component for the topical skin composition, packaging for thedispensing component, and instructions for using the dispenser andtopical skin composition.

In some embodiments, the present disclosure provides a topical skincomposition comprising (i) rose oil; (ii) cannabidiol (CBD), and (iii) ahumectant, wherein the composition is incorporated into a productselected from the group consisting of an eye cream, a serum, a facemask, and a lotion.

In some embodiments, the present disclosure provides products selectedfrom the group consisting of an eye cream, a serum, a face mask, and alotion, wherein a topical skin care composition comprising (i) rose oil;(ii) CBD, and (iii) a humectant is incorporated into any one of saidproducts.

In some embodiments, provided herein is a topical skin care compositioncomprising 2% v/v rose oil, 1% w/v CBD, 54% v/v glycerin, 1% v/vhyaluronic acid, 0.1% v/v tocopherol, 3% v/v phospholipids, and 10% v/vcaprylic/capric triglycerides, wherein the rose oil is an extract fromRhododendron ferrugineum.

In some embodiments, provided herein is a topical skin care compositioncomprising 2% v/v rose oil, 1% v/v CBD, 54% v/v glycerin, 1% v/vhyaluronic acid, 0.1% v/v tocopherol, 3% v/v phospholipids, and 10% v/vcaprylic/capric triglycerides, wherein the rose oil is an extract fromRhododendron ferrugineum.

In some embodiments, provided herein is a topical skin care compositioncomprising 2% v/v rose oil, 1% w/v CBD, 54% v/v glycerin, 1% v/vhyaluronic acid, 3% v/v phospholipids, and 10% v/v caprylic/caprictriglycerides, wherein the rose oil is an extract from Rhododendronferrugineum.

In some embodiments, provided herein is a topical skin care compositioncomprising 2% v/v rose oil, 1% v/v CBD, 54% v/v glycerin, 1% v/vhyaluronic acid, 3% v/v phospholipids, and 10% v/v caprylic/caprictriglycerides, wherein the rose oil is an extract from Rhododendronferrugineum.

DESCRIPTION OF THE DRAWINGS

FIG. 1 shows representative images of the effect of compounds S-863d andS-863g on the migration of KSCs.

DETAILED DESCRIPTION OF THE INVENTION Definitions

As used herein, the verb “comprise” is used in this description and inthe claims and its conjugations are used in its non-limiting sense tomean that items following the word are included, but items notspecifically mentioned are not excluded.

As used herein, the term “about” refers to plus or minus 10% of thereferenced number unless otherwise stated or otherwise evident by thecontext, and except where such a range would exceed 100% of a possiblevalue, or fall below 0% of a possible value, such as less than 0%content of an ingredient, or more than 100% of the total contents of acomposition. For example, reference to an absolute content ofcannabidiol of “about 1% w/w” means that cannabidiol can be present atany amount ranging from 0.9% to 1.1% content by weight.

The term “a” or “an” refers to one or more of that entity; for example,“a gene” refers to one or more genes or at least one gene. As such, theterms “a” (or “an”), “one or more” and “at least one” are usedinterchangeably herein. In addition, reference to “an element” by theindefinite article “a” or “an” does not exclude the possibility thatmore than one of the elements is present, unless the context clearlyrequires that there is one and only one of the elements.

As used herein, the term “skin” refers to any of the layers of the skin,including the epidermis, dermis, and hypodermis. The epidermis has fivesub-layers, including the stratum corneum, stratum lucidum, stratumgranulosum, stratum spinosum, and stratum basale, which are listed fromthe outermost sub-layer to the innermost sub-layer. For example, thestratum corneum is the skin's surface.

As used herein, the term “skin care composition” refers to anyformulation that is applied to the skin.

Various concentration expressions, including volume concentrations,weight concentrations, and mass concentrations, are utilized to describethe percentage of a component in a solution. Volume concentration hasunits of % v/v, where v/v is volume per volume. If a solution containsκ% v/v of a component, 5 mL of the component is in a total solution of100 mL. Weight concentration of a solution is expressed as % w/w, wherew/w is weight per weight. If a solution contains 30% w/w of sodiumchloride, the solution contains 30 g of sodium chloride and 70 g ofsolvent. Mass concentration of a solution is expressed as % w/v, wherew/v is weight per volume. If 1 g of sodium chloride is dissolved in asolution with a total volume of 100 mL, a 1% w/v sodium chloridesolution has been made.

In some embodiments, the disclosure describes “topical application” ofthe skin care composition. As defined herein, “topical application” isapplication of a composition to the skin.

As used herein, the term “cosmetic vehicle” refers to any molecule,group of molecules, or biomolecule used to deliver ingredients of theskin composition to the skin. Ingredients may be active ingredients oradditional ingredients described herein. Non-limiting examples ofcosmetic vehicles include liposomes, nanosomes, emulsions,microemulsions, nanocapsules, solid lipid nanoparticles, andnanocrystals.

In some embodiments, the skin care compositions contain humectants. Asused herein, the term “humectant” refers to a hygroscopic substance,which moisturizes the skin. Non-limiting examples of humectants areprovided throughout the disclosure.

The disclosure provides plant parts. As used herein, the term “plantpart” refers to any part of a plant including but not limited to theembryo, shoot, root, stem, seed, stipule, leaf, petal, flower,inflorescence, bud, ovule, bract, trichome, branch, petiole, internode,bark, pubescence, tiller, rhizome, frond, blade, pollen, stamen,mesocarp, epicarp, endosperm, spermoderm, disk, embryo, and the like.The two main parts of plants grown in some sort of media, such as soilor vermiculite, are often referred to as the “above-ground” part, alsooften referred to as the “shoots”, and the “below-ground” part, alsooften referred to as the “roots”.

Unless otherwise noted, references to cannabidiol (CBD) in the presentdisclosure should be understood as references to both the acidic (CBDA)and decarboxylated (CBD) versions of the cannabidiol. For example,references to CBD should be understood as references to the combined CBDand CBDA content, accounting for weight loss during decarboxylation.

In some embodiments, the compositions contain cannabidiol (CBD). As usedherein, CBD refers to synthetic CBD or to a Cannabis extract, whichcontains between 1% w/w to 100% w/w CBD. In some embodiments, pure CBDis utilized in the compositions of the disclosure. As used herein, pureCBD refers to synthetic CBD or a CBD extract, which contains betweenabout 80% w/w to about 100% w/w CBD.

As used herein, regulating a skin condition includes delaying,minimizing, effacing, or preventing visible or tactile discontinuitiesin skin or both visible and tactile discontinuities in the skin (e.g.,texture irregularities in the skin which may be detected visually or byfeel), including signs of skin aging.

Skin Care Compositions

In some embodiments, the disclosure provides skin care compositions.Skin care compositions contain active ingredients and optionally containadditional ingredients, which are described below. In some embodiments,the skin care compositions are delivered by a cosmetic vehicle topicallyto the skin. In some embodiments, the skin care compositions areincorporated into products as described throughout this disclosure. Insome embodiments, the invention provides luxury and designer skin careproducts enriched with CBD and rose oil.

In some embodiments, the disclosure provides skin care compositions thatare Halal certified.

In some embodiments, the disclosure provides skin care compositions thatdo not contain any substances that are carcinogenic, mutagenic or toxicfor reproduction.

In some embodiments, the disclosure provides skin care compositions thatdo not contain any allergenic substances according to the applicablegovernmental regulations for cosmetics.

In some embodiments, the disclosure provides skin care compositions thatare not subjected to an irradiation step.

In some embodiments, the disclosure provides skin care compositions forwhich their development and/or manufacturing did not involve the use ofany animal originating and/or animal derived components.

In some embodiments, the disclosure provides skin care compositions thatdo not contain any ingredients subject to the Nagoya Protocol.

Active Ingredients

The present disclosure teaches various skin compositions containing oneor more active ingredients. In some embodiments, the active ingredientsare rose oil, cannabidiol, and a humectant.

In some embodiments, the present disclosure teaches skin compositionscontaining up to 5% w/v CBD, up to 5% v/v rose oil, and up to 5% v/v ofa humectant. In some embodiments, the present disclosure teaches skincompositions containing up to 5% v/v CBD, up to 5% v/v rose oil, and upto 5% v/v of a humectant. In some embodiments, the present disclosureteaches skin compositions containing 1% w/v CBD, 2% v/v rose oil, and 1%v/v humectant. In some embodiments, the present disclosure teaches skincompositions containing 1% v/v CBD, 2% v/v rose oil, and 1% v/vhumectant. In some embodiments, the present disclosure teaches skincompositions containing 1% w/w CBD, 2% v/v rose oil, and 1% v/vhumectant.

Rose Oil

In some embodiments, the present disclosure teaches compositions thatcontain the active ingredient rose oil. In some embodiments, rose oilcauses pain relief, reduces anxiety, reduces stress, eases depression,reduces acne, and exhibits anti-bacterial and anti-fungal properties.

In some embodiments, the compositions of the disclosure contain about 0%to about 5 rose oil. In some embodiments, the compositions contain up toabout 0.5%, or up to about 1%, or up to about 1.5%, or up to about 2.0%,or up to about 2.5%, or up to about 3.0%, or up to about 3.5%, or up toabout 4.0%, or up to about 4.5%, or up to about 5% rose oil.

In some embodiments, rose oil is an extract from a plant selected fromthe group consisting of Rosa damascena, Rosa centifolia, Rhododendronferrugineum, Rhododendron brachycarpum, Rosa gallica, Rosa gallicaLinne, Rosa gallica var. aegyptiaca, and Rhododendron hirsutum. In someembodiments, rose oil is an extract of Rosa damascena. In someembodiments, rose oil is an extract of Rhododendron ferrugineum.

In some embodiments, rose oil is a plant meristematic stem cell extractfrom Rosa damascena, Rosa centifolia, Rosa gallica, Rosa gallica Linne,Rosa gallica var. aegyptiaca, Rhododendron ferrugineum, Rhododendronbrachycarpum, or Rhododendron hirsutum. Meristematic stem cells areundifferentiated cells serving as the origin of plant vitality, as theymaintain themselves while providing a steady supply of precursor cellsto form differentiated tissues and organs in plants. Plant meristematiccells contain epigenetic factors similar to those of adult human stemcells. Methods of making plant meristematic cell extracts are found inInternational Publication No. 2014/167557 (published Oct. 16, 2014),which is incorporated by reference herein in its entirety.

In some embodiments, rose oil is selected from the group consisting of ameristematic stem cell extract from Rhododendron ferrugineum, Alp Rose(Mibelle Biochemistry), AlpineRoseActive™ (Mibelle Biochemistry), andRose Absolute.

In some embodiments, rose oil is used in combination with an alternativeplant extract. In some embodiments, rose oil is replaced with analternative plant extract. In some embodiments, the alternative plantextract contains stem cells. Non-limiting examples of plant extracts areselected from the group consisting of Bellis perrenis, Leontopodiumalpinum, Malus domestica, Catharanthus roseus, Catharanthus tincorius,Eriodictyon californicum, Camellia sinensin, Marrubium vulgare, Schinusmolle, Camellia japonica, Schisandar chinensin, Oenothera biennis,Menyanthes trifoliate, Michelia magnifica, Xylosma japonicum, Prunuscerasifera, Nyssa sinensis, Chimonanthus praecox, Sassafras tzumu, Inulahelianthus-aquatica, Capparis bodinieri, Passiflora caerulea, Galiumaparine, Boehmeria platyphylla, Colquhounia coccinea, Sageretia rugosa,Jasminum stephanense, Antirrhinum majus, Daphniphyllum oldhamii, Cuscutachinensis, Salix variegate, Osmanthus parvifolius, Euphorbia trigona,Calliandra haematocephala, Excoecaria acerifolia, Dianthus chinensis,Myriophyllum spicatum, Nymphoides peltatum, Prunus salicina, Solanumcoagulans, Elaeis guineensis, Rhododendron moulmainense, Spatholobussuberectus, Artabotrys hexapetalus, Hibiscus syriacus, Loniceracalcarata, Hydnocarpus hainanensis, Ilex fragilis, Antidesma venosum,Acacia pennata ssp. Kerrii, Althaea rosea, Millettia velutina, Themedajaponica, Dalbergia hancei, Ipomoea batatas, Photinia glomerata,Hippophae rhamnoides, Azadirachta indica, Karelinia caspica, Bauhiniatouranensis, Eriobotrya japonicas, Anaphalis contorta, and Cratoxylumprunifolium.

In some embodiments, AlpineRoseActive™ is used in the compositions ofthe disclosure. AlpineRoseActive™ is an extract of Rhododendronferriguneum. AlpineRoseActive™ is not an aromatic oil. This extractprotects exerts an antiviral effect against herpes simplex and protectsagainst protein oxidation.

In some embodiments, rose oil is replaced with daisy plant extract. Insome embodiments, rose oil is used in addition to a daisy plant extract.Non-limiting examples of daisy plant extracts are selected from thegroup consisting of Bellis perennis, Leucanthemum vulgare, andChrysanthemum leucanthemum.

In some embodiments, rose oil is replaced with orchid extracts. In someembodiments, rose oil is used in addition to an orchid extract. In someembodiments, the orchid extracts contain stem cells. Non-limitingexamples of orchid extracts are selected from the group consisting ofCalanthe discolor, Vanda coeurela, Papillionanthes teres, and Vandadenisoniona. In some embodiments, a product containing orchid extractfrom Calanthe discolor, ORCHISTEM™, is included in the compositions ofthe disclosure. In some embodiments, orchid extracts increase cell tocell communication, stimulate epidermal growth factor, and increaseelastin and collagen production in skin.

In some embodiments, rose oil or an alternative plant extract isproduced according to known methods in the art. The extract can be fromthe whole plant or plant parts (e.g., root, bark, sap, stem, leaf,flower, seed, leaf, stem, root, flower, seed, sap, bark, etc.). Theextract can be an aqueous extract or a non-aqueous extract. The extractcan be extracted with alcohol (e.g., methanol, ethanol propanol,butanol, etc.), glycols, oils, or water.

Cannabidiol

In some embodiments, the present disclosure teaches products thatcontain the active ingredient cannabidiol. In some embodiments,cannabidiol is extracted from Cannabis plants to form a CBD extract.Non-limiting examples of Cannabis plants include Cannabis sativa,Cannabis indica, or Cannabis ruderalis. In some embodiments, cannabidiolis extracted from hybrid varieties of Cannabis. Cannabidiol is extractedfrom Cannabis plants according to known methods in the art. Non-limitingextraction methods include sonication, heating under reflux, soxhletextraction, solid-phase micro-extraction, supercritical-fluidextraction, pressurized-liquid extraction, microwave-assistedextraction, solid-phase extraction, and surfactant-mediated techniques.In some embodiments, the steps for extraction include, but are notlimited, to pre-washing, drying of plant parts or freeze drying, andgrinding to obtain homogenous extracted plant samples.

In some embodiments, cannabidiol is extracted using an alcohol-basedextraction. In some embodiments, cannabidiol is extracted with ethanol.In some embodiments, cannabidiol is obtained using a supercriticalcarbon dioxide based extraction. Methods for extraction of CBD fromCannabis plants are described in the following patent documents whichare incorporated by reference in their entirety herein: U.S. PublicationNo. 2019/0231833 A1, (published Aug. 1, 2019), International PublicationNo. 2019/020738 (published Jan. 31, 2019), International Publication No.2004/016277 A1 (published Feb. 26, 2004), and U.S. Publication No.2019/0160393 A1 (published May 30, 2019).

In some embodiments, the compositions of the disclosure use CBDextracts. In some embodiments, a CBD extract contains from about 1% w/wto about 100% w/w of CBD. In some embodiments, the CBD extract containsabout 1% w/w CBD, or about 2% w/w CBD, or about 3% w/w CBD, or about 4%w/w CBD, or about 5% w/w CBD, or about 10% w/w CBD, or about 20% w/wCBD, or about 30% w/w CBD, or about 40% w/w CBD, or about 50% w/w CBD,or about 60% w/w CBD, or about 70% w/w CBD, or about 80% w/w CBD, orabout 90% w/w CBD, or about 95% w/w CBD, or about 96% w/w CBD, or about97% w/w CBD, or about 98% w/w CBD, or about 99% w/w CBD, or about 100%w/w CBD. In some embodiments, the CBD extract contains about 99.3% w/wCBD.

In some embodiments, CBD or a CBD extract is produced from the wholeCannabis plant. In some embodiments, CBD or a CBD extract is producedfrom the above-surface plant parts of Cannabis plants. The above-surfaceplant parts are also known as plant tops, above ground plant parts andplant shoots. The shoots of plants generally refer to a plant's stems,leaves, flowers and fruit. In some embodiments, CBD or a CBD extract isproduced from one or more Cannabis plant parts (e.g., root, bark, sap,stem, leaf, flower, seed, leaf, stem, root, flower, seed, sap, bark,etc.). In some embodiments, CBD or CBD extract is produced from Cannabisflowers. In some embodiments, CBD or CBD extract is produced from thestems and leaves of a Cannabis plant.

In some embodiments, the CBD extract is CBD Isolate Max™ (Kazmira™).

In some embodiments, CBD extracts contain one or more cannabinoids.Non-limiting examples of cannabinoids include cannabidiol (CBD),Cannabinol (CBN), Cannabigerol (CBG), Cannabichromene (CBC),Cannabicyclol (CBL), Cannabivarin (CBV), Tetrahydrocannabivarin (THCV),Cannabidivarin (CBDV), Cannabichromevarin (CBCV), Cannabigerovarin(CBGV), Cannabigerol Monomethyl Ether (CBGM), and Tetrahydrocannabinol(THC), cannabidiolic acid (CBDA), and tetrahydrocannabinolic acid(THCA).

In some embodiments, the CBD extract contains CBDV. In some embodiments,the CBD extract contains between about 0% w/w and about 5% w/w CBDV. Insome embodiments, the CBD extract contains between about 0.1% w/w andabout 5% w/w CBDV. In some embodiments, the CBD extract contains about0.10% w/w, about 0.15% w/w, about 0.19% w/w, about 0.20% w/w, about0.25% w/w, about 0.30% w/w, about 0.35% w/w, about 0.40% w/w, about0.45% w/w, about 0.5% w/w, about 0.6% w/w, about 0.7% w/w, about 0.8%w/w, about 0.9% w/w, about 1.0% w/w, about 1.5% w/w, about 2.0% w/w,about 2.5% w/w, about 3.0% w/w, about 3.5% w/w, about 4.0% w/w, about4.5% w/w, or about 5.0% w/w CBDV.

In some embodiments, the CBD extract contains one or more terpenes.Terpenes are a class of compounds composed of five-carbon isoprene unitsthat have the molecular formula (C₅H₈)_(n), where n dictates the numberof isoprene units. Non-limiting examples of terpenes includealpha-cedrene, alpha-humulene, alpha-pinene, alpha-terpinene,beta-myrcene, beta-pinene, borneol, camphene, camphor, caryophylleneoxide, cedrol, alpha-bisabolol, alpha-phellandrene, isopulegol,cis-nerolidol, 3-carene, fenchyl alcohol, hexahydrothymol, eucalyptol,isoborneol, farnesene, fenchone, gamma-terpinene, geraniol, geranylacetate, humulene, guaiol, limonene, linalool, nerol, ocimene,alpha-phellandrene, pulegone, sabinene, sabinene hydrate, terpineol,terpinolene, trans-caryophyllene, β-caryophyllene, trans-nerolidol, andvalencene. In some embodiments, the CBD extract containstrans-nerolidol. In some embodiments, the CBD extract containsalpha-bisabolol. In some embodiments, the CBD extract contains linalool.In some embodiments, the CBD extract contains β-caryophyllene. In someembodiments, the CBD extract contains guaiol. In some embodiments, theCBD extract contains humulene. In some embodiments, the CBD extractcontains limonene. In some embodiments, the CBD extract containsalpha-phellandrene.

In some embodiments, the CBD extract contains less than about 1.0% w/wterpenes. In some embodiments the CBD extract contains less than about0.01% w/w, about 0.02% w/w, about 0.03% w/w, about 0.04% w/w, about 0.05w/w, about 0.06% w/w, about 0.07% w/w, about 0.08% w/w, about 0.09% w/w,about 0.1% w/w, about 0.2% w/w, about 0.3% w/w, about 0.4% w/w, about0.5% w/w, about 0.6% w/w, about 0.7% w/w, about 0.8% w/w, about 0.9%w/w, or about 1.0% w/w terpenes.

In some embodiments, cannabidiol is produced synthetically. As describedherein, synthetic cannabidiol includes CBD analogs, CBD salts, modifiedCBD, and propyl cannabinoids (CBDv). Synthetic CBD has the same orsimilar therapeutic effects as naturally occurring CBD when administeredto the subjects. Patent documents, such as U.S. Publication No.2019/0031601 (published Jan. 31, 2019), U.S. Pat. No. 9,447,019 (issuedSep. 20, 2016), and U.S. Publication No. 2015/0320698 (published Nov.12, 2015), which describe synthetic cannabinoids are incorporated byreference herein in their entirety.

Methods for cannabidiol synthesis are described in the following patentdocuments, which are incorporated by reference in their entirety herein:EP Publication No. 2578561 A1 (published Apr. 10, 2013), U.S.Publication No. 2017/0008868 A1 (published Aug. 28, 2018). In someembodiments, cannabidiol is produced in microorganisms. Methods forproducing cannabidiol in microorganisms are described in U.S.Publication No. 2016/0010126 A1 (published Jan. 14, 2016) andInternational Publication No. 2017/139496 (published Aug. 17, 2016),which are incorporated by reference in their entireties, herein. In someembodiments, CBD is obtained from commercial sources such as BluebirdBotanicals, CBDistillery™, or ExtractLabs™.

In some embodiments, a CBD extract or synthetic CBD is pure CBD. In someembodiments, pure CBD contains from about 80% w/w to about 100% w/w ofCBD. In some embodiments, pure CBD contains about 80% w/w, or about 85w/w, or about 90% w/w, or about 95% w/w, or about 96% w/w, or about 97%w/w, or about 98% w/w, or about 99% w/w, or about 100% w/w CBD.

In some embodiments, the compositions of the disclosure containcannabidiolic acid (CBDA) in addition to CBD. In some embodiments, CBDAis converted to CBD by decarboxylation according to the reaction below:

In some embodiments, CBD is obtained from CBDA by heating CBDA totemperatures above 270° F.

In some embodiments, the resultant CBD extracts are processed to removeunwanted co-extracted plant material and phytochemicals, and/or toremove THC.

In some embodiments, the CBD used in the compositions of the disclosureis isolated as a crystalline solid.

In some embodiments, the CBD used in the compositions of the disclosureis tested for confirmation and certification as to its purity and/or asbeing free from certain contaminants.

In some embodiments, the CBD used in the compositions of the disclosureare tested for one or more of residual solvents or other impurities.

In some embodiments, farm-to-product traceability is employed throughoutthe entirety of the processes utilized to grow, harvest, extract andpurify the CBD used in the compositions of the disclosure.

In some embodiments, the compositions of the disclosure contain fromabout 0% w/w to about 5% w/w CBD. In some embodiments, the compositionsof the disclosure contain from about 0.1% w/w to about 5% w/w CBD. Insome embodiments, the CBD is an extract. In some embodiments, the CBD issynthetic. In some embodiments, the compositions contain up to about0.5% w/w, or up to about 1% w/w, or up to about 1.5% w/w, or up to about2.0% w/w, or up to about 2.5% w/w, or up to about 3.0% w/w, or up toabout 3.5% w/w, or up to about 4.0% w/w, or up to about 4.5% w/w, or upto about 5% w/w CBD.

In some embodiments, the compositions of the disclosure contain fromabout 0% w/v to about 5% w/v CBD. In some embodiments, the compositionsof the disclosure contain from about 0.1% w/v to about 5% w/v CBD. Insome embodiments, the CBD is an extract. In some embodiments, the CBD issynthetic. In some embodiments, the compositions contain up to about0.5% w/v, or up to about 1% w/v, or up to about 1.5% w/v, or up to about2.0% w/v, or up to about 2.5% w/v, or up to about 3.0% w/v, or up toabout 3.5% w/v, or up to about 4.0% w/v, or up to about 4.5% w/v, or upto about 5% w/v CBD.

In some embodiments, the compositions of the disclosure contain fromabout 0 v/v to about 5% v/v CBD. In some embodiments, the compositionsof the disclosure contain from about 0.1% v/v to about 5% v/v CBD. Insome embodiments, the CBD is an extract. In some embodiments, the CBD issynthetic. In some embodiments, the compositions contain up to about0.5% v/v, or up to about 1% v/v, or up to about 1.5% v/v, or up to about2.0% v/v, or up to about 2.5% v/v, or up to about 3.0% v/v, or up toabout 3.5% v/v, or up to about 4.0% v/v, or up to about 4.5% v/v, or upto about 5% v/v CBD.

Cannabidiol is associated with several health benefits. Examples includepain relief and reduction of anxiety, depression, insomnia, migraines,and acne.

The high lipophilicity of CBD (structure shown below) makes delivery ofthis compound to the skin challenging.

In some embodiments, the compositions described in the presentdisclosure allow accumulation of CBD in the skin.

Humectants

In some embodiments, the present disclosure teaches compositions thatcontain a humectant as an active ingredient. In some embodiments,humectants cause increased elasticity, smoothness, and hydration of theskin. In some embodiments, the humectant glyceryl glucoside (Glycoin®)is used in the products of the disclosure. In some embodiments, glycerylglucoside is isolated from Myrothamnus flabellifolia or Spirulina.Glyceryl glucoside is a multifunctional anti-aging and cell-boostingingredient. Glyceryl glucoside stimulates aged skin cells by boostingand revitalizing their metabolic activity, and stimulating ATP synthesisand anti-oxidant activity. In some embodiments, the compositions of thedisclosure contain about 0% v/v to about 5% v/v glyceryl glucoside. Insome embodiments, the compositions contain up to about 0.5% v/v, or upto about 1% v/v, or up to about 1.5% v/v, or up to about 2.0% v/v, or upto about 2.5% v/v, or up to about 3.0% v/v, or up to about 3.5% v/v, orup to about 4.0% v/v, or up to about 4.5% v/v, or up to about 5% v/vglyceryl glucoside. In some embodiments, glyceryl glucoside in thecompositions of the disclosure stimulates cell renewal, growth factorsand ATP synthesis. In some embodiments, glyceryl glucoside in thecompositions of the disclosure boosts anti-oxidative enzymes.Non-limiting examples of anti-oxidative enzymes include superoxidedismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and catalase (CAT).In some embodiments, glyceryl glucoside in the compositions of thedisclosure increases hydration of the skin. In some embodiments,glyceryl glucoside in the compositions of the disclosure increases skinelasticity, skin smoothness, skin thickness, and combinations thereof.In some embodiments, glyceryl glucoside reduces sunburn and skinredness. In some embodiments, glyceryl glucoside causes whitening andlightening of pigmented skin. In some embodiments, glyceryl glucosidestimulates tissue repair and wound healing.

In some embodiments, the present disclosure teaches compositions thatcontain the humectant hyaluronic acid. Hyaluronic acid promoteshydration and can hold up to 1000 times its weight in water. Hyaluronicacid is a glycosaminoglycan which is used to prevent aging, includingwrinkles around the eyes. In some embodiments, the compositions of thedisclosure contain about 0% v/v to about 5% v/v hyaluronic acid. In someembodiments, the compositions contain up to about 0.5% v/v, or up toabout 1% v/v, or up to about 1.5% v/v, or up to about 2.0% v/v, or up toabout 2.5% v/v, or up to about 3.0% v/v, or up to about 3.5% v/v, or upto about 4.0% v/v, or up to about 4.5% v/v, or up to about 5% v/vhyaluronic acid. In some embodiments, the compositions of the disclosurecontain hyaluronic acid, which is released over time. In someembodiments, hyaluronic acid is released over 48 hours or more. In someembodiments, hyaluronic acid is provided as Hyalusphere™. Hyalusphere™is a high molecular weight hyaluronic acid. In some embodiments, thecompositions of the disclosure contain Hyalusphere™, which is releasedover time. In some embodiments, Hyalusphere™ is released over 48 hoursor more. In some embodiments, hyaluronic acid is used in creams orlotions, including but not limited to face cream and eye cream. In someembodiments, hyaluronic acid is not used with oils. In some embodiments,a hyaluronic acid derivative is used as a humectant. In someembodiments, PrimalHyal™ is used as a humectant. PrimalHyal™ isresistant to hyaluronidases and penetrates twice as deep into the skinas hyaluronic acid.

In some embodiments, the present disclosure teaches compositions thatcontain an extract of Aloe vera as a humectant. In some embodiments,about 0% v/v to about 5% v/v of the composition contains Aloe veraextract. In some embodiments, the compositions contain up to about 0.5%v/v, or up to about 1% v/v, or up to about 1.5% v/v, or up to about 2.0%v/v, or up to about 2.5% v/v, or up to about 3.0% v/v, or up to about3.5% v/v, or up to about 4.0% v/v, or up to about 4.5% v/v, or up toabout 5% v/v Aloe vera extract.

In some embodiments, alternative humectants are used in the products ofthe disclosure. Non-limiting examples of humectants include amino acids,chondroitin sulfate, diglycerol, erythritol, fructose, glucose,glycerol, glycerol polymers, glycol, 1,2,6-hexanetriol, honey,hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolyzate,inositol, lactitol, maltitol, maltose, mannitol, natural humectantfactor, PEG-15-butanediol, polyglyceryl sorbitol, salts ofpyrrolidonecarboxylic acid, potassium PCA, propylene glycol, saccharideisomerate, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose,urea and xylitol.

Additional Ingredients

The compositions of the present disclosure can also include any one of,any combination of, or all of the following additional ingredients:water, a chelating agent, a UV absorption agent, a moisturizing agent, apreservative, a thickening agent, a silicone containing compound, anessential oil, a structuring agent, a vitamin, a pharmaceuticalingredient, or an antioxidant, or any combination of such ingredients ormixtures of such ingredients. In certain aspects, the composition caninclude at least two, three, four, five, six, seven, eight, nine, ten,or all of these additional ingredients. U.S. Pat. No. 9,814,670 (issuedNov. 14, 2017) describes many of these ingredients and is incorporatedby reference in its entirety herein.

In some embodiments, the compositions of the disclosure contain water.

Chelating Agents

In some embodiments, the compositions of the disclosure containchelating agents. Non-limiting examples of chelating agents includedisodium ethylenediaminetetraacetic acid (EDTA) and tetrasodium EDTA.

UV Absorption Agents

In some embodiments, the compositions of the present disclosure includeUV absorption agents. UV absorption agents include chemical and physicalsunblocks. Non-limiting examples of chemical sunblocks that can be usedinclude para-aminobenzoic acid (PABA), PABA esters (glyceryl PABA,amyldimethyl PABA and octyldimethyl PABA), butyl PABA, ethyl PABA, ethyldihydroxypropyl PABA, benzophenones (oxybenzone, sulisobenzone,benzophenone, and benzophenone-1 through 12), cinnamates (octylmethoxycinnamate, isoamyl p-methoxycinnamate, octylmethoxy cinnamate,cinoxate, diisopropyl methyl cinnamate, DEA-methoxycinnamate, ethyldiisopropylcinnamate, glyceryl octanoate dimethoxycinnamate and ethylmethoxycinnamate), cinnamate esters, salicylates (homomethyl salicylate,benzyl salicylate, glycol salicylate, isopropylbenzyl salicylate, etc.),anthranilates, ethyl urocanate, homosalate, octisalate, dibenzoylmethanederivatives (e.g., avobenzone), octocrylene, octyl triazone, digalloyltrioleate, glyceryl aminobenzoate, lawsone with dihydroxyacetone,ethylhexyl triazone, dioctyl butamido triazone, benzylidene malonatepolysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyldibenzimidazole tetrasulfonate, diethylamino hydroxybenzoyl hexylbenzoate, bis-diethylamino hydroxybenzoyl benzoate, bisbenzoxazoylphenyl ethylhexylimino-triazine, drometrizole trisiloxane,methylene bis-benzotriazolyl tetramethylbutylphenol, andbis-ethylhexyloxyphenol methoxyphenyltriazine, 4-methylbenzylidenecamphor, and isopentyl-4-methoxycinnamate. Non-limiting examples ofphysical sunblocks include, kaolin, talc, petrolatum and metal oxides(e.g., titanium dioxide and zinc oxide).

Emollients

In some embodiments, the compositions of the disclosure contain one ormore emollients. Emollients are lubricating ingredients that make theskin soft and smooth and help the skin to retain moisture. Non-limitingexamples of emollients include vegetable oils, mineral oils, sheabutter, cocoa butter, petrolatum, cholesterol, silicone, and animal oils(including emu, mink, and lanolin).

Moisturizing Agent

In some embodiments, the compositions of the disclosure containmoisturizing agents. Non-limiting examples of moisturizing agents thatcan be used with the compositions of the present invention include aminoacids, chondroitin sulfate, diglycerin, erythritol, fructose, glucose,glycerin, glycerol polymers, glycol, 1,2,6-hexanetriol, honey,hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolysate,inositol, lactitol, maltitol, maltose, mannitol, natural moisturizingfactor, PEG-15 butanediol, polyglyceryl sorbitol, salts of pyrrolidonecarboxylic acid, potassium PCA, propylene glycol, sodium glucuronate,sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.

Other examples include acetylated lanolin, acetylated lanolin alcohol,alanine, algae extract, aloe barbadensis, aloe-barbadensis extract, aloebarbadensis gel, althea officinalis extract, apricot (Prunus armeniaca)kernel oil, arginine, arginine aspartate, Arnica montana extract,aspartic acid, avocado (Persea gratissima) oil, barrier sphingolipids,butyl alcohol, beeswax, behenyl alcohol, beta-sitosterol, birch (Betulaalba) bark extract, borage (Borago officinalis) extract, butcherbroom(Ruscus aculeatus) extract, butylene glycol, Calendula officinalisextract, Calendula officinalis oil, candelilla (Euphorbia cerifera) wax,canola oil, caprylic/capric triglyceride, cardamom (Elettariacardamomum) oil, carnauba (Copernicia cerifera) wax, carrot (Daucuscarota sativa) oil, castor (Ricinus communis) oil, ceramides, ceresin,ceteareth-5, ceteareth-12, ceteareth-20, cetearyl octanoate, ceteth-20,ceteth-24, cetyl acetate, cetyl octanoate, cetyl palmitate, chamomile(Anthemis nobilis) oil, cholesterol, cholesterol esters, cholesterylhydroxystearate, citric acid, clary (Salvia sclarea) oil, cocoa(Theobroma cacao) butter, coco-caprylate/caprate, coconut (Cocosnucifera) oil, collagen, collagen amino acids, corn (Zea mays) oil,fatty acids, decyl oleate, dimethicone copolyol, dimethiconol, dioctyladipate, dioctyl succinate, dipentaerythrityl hexacaprylate/hexacaprate,DNA, erythritol, ethoxydiglycol, ethyl linoleate, Eucalyptus globulusoil, evening primrose (Oenothera biennis) oil, fatty acids, geraniummaculatum oil, glucosamine, glucose glutamate, glutamic acid,glycereth-26, glycerin, glycerol, glyceryl distearate, glycerylhydroxystearate, glyceryl laurate, glyceryl linoleate, glycerylmyristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE,glycine, glycol stearate, glycol stearate SE, glycosaminoglycans, grape(Vitis vinifera) seed oil, hazel (Corylus americana) nut oil, hazel(Corylus avellana) nut oil, hexylene glycol, hyaluronic acid, hybridsafflower (Carthamus tinctorius) oil, hydrogenated castor oil,hydrogenated coco-glycerides, hydrogenated coconut oil, hydrogenatedlanolin, hydrogenated lecithin, hydrogenated palm glyceride,hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenatedtallow glyceride, hydrogenated vegetable oil, hydrolyzed collagen,hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin,hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocetylstearate, isocetyl stearoyl stearate, isodecyl oleate, isopropylisostearate, isopropyl lanolate, isopropyl myristate, isopropylpalmitate, isopropyl stearate, isostearamide DEA, isostearic acid,isostearyl lactate, isostearyl neopentanoate, jasmine (Jasminumofficinale) oil, jojoba (Buxus chinensis) oil, kelp, kukui (Aleuritesmoluccana) nut oil, lactamide MEA, laneth-16, laneth-10 acetate,lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax,lavender (Lavandula angustifolia) oil, lecithin, lemon (Citrus medicalimonum) oil, linoleic acid, linolenic acid, macadamia ternifolia nutoil, maltitol, matricaria (Chamomilla recutita) oil, methyl glucosesesquistearate, methylsilanol PCA, mineral oil, mink oil, mortierellaoil, myristyl lactate, myristyl myristate, myristyl propionate,neopentyl glycol dicaprylate/dicaprate, octyldodecanol, octyldodecylmyristate, octyldodecyl stearoyl stearate, octyl hydroxystearate, octylpalmitate, octyl salicylate, octyl stearate, oleic acid, olive (Oleaeuropaea) oil, orange (Citrus aurantium dulcis) oil, palm (Elaeisguineensis) oil, palmitic acid, pantethine, panthenol, panthenyl ethylether, paraffin, PCA, peach (Prunus persica) kernel oil, peanut (Arachishypogaea) oil, PEG-8 C12-18 ester, PEG-15 cocamine, PEG-150 distearate,PEG-60 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glycerylstearate, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated castor oil,PEG-60 hydrogenated castor oil, PEG-20 methyl glucose sesquistearate,PEG-40 sorbitan peroleate, PEG-5 soy sterol, PEG-10 soy sterol, PEG-2stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40stearate, PEG-50 stearate, PEG-100 stearate, PEG-150 stearate,pentadecalactone, peppermint (Mentha piperita) oil, petrolatum,phospholipids, polyamino sugar condensate, polyglyceryl-3 diisostearate,polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60,polysorbate 80, polysorbate 85, potassium myristate, potassiumpalmitate, propylene glycol, propylene glycol dicaprylate/dicaprate,propylene glycol dioctanoate, propylene glycol dipelargonate, propyleneglycol laurate, propylene glycol stearate, propylene glycol stearate SE,PVP, pyridoxine dipalmitate, retinol, retinol palmitate, rice (Oryzasativa) bran oil, RNA, rosemary (Rosmarinus officinalis) oil, rose oil,safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) oil,sandalwood (Santalum album) oil, serine, serum protein, sesame (Sesamumindicum) oil, shea butter (Butyrospermum parkii), silk powder, sodiumchondroitin sulfate, sodium hyaluronate, sodium lactate, sodiumpalmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitanlaurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate,sorbitan stearate, sorbitol, soybean (Glycine soja) oil, sphingolipids,squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxydimethicone, stearoxytrimethylsilane, stearyl alcohol, stearylglycyrrhetinate, stearyl heptanoate, stearyl stearate, sunflower(Helianthus annuus) seed oil, sweet almond (Prunus amygdalus dulcis)oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryllinoleate, tribehenin, tridecyl neopentanoate, tridecyl stearate,triethanolamine, tristearin, urea, vegetable oil, water, waxes, wheat(Triticum vulgare) germ oil, and ylang ylang (Cananga odorata) oil.

In some embodiments, the compositions of the disclosure containtocopherol. In some embodiments, the compositions of the disclosurecontain tocopherol at a concentration between about 0% v/v and about 5%v/v. In some embodiments, the compositions of the disclosure containtocopherol at a concentration between about 0.1% v/v and about 5% v/v.In some embodiments, the compositions of the disclosure containtocopherol at about 0.01% v/v, about 0.02% v/v, about 0.03% v/v, about0.04% v/v, about 0.05% v/v, about 0.06% v/v, about 0.07% v/v, about0.08% v/v, about 0.09% v/v, about 0.10% v/v, about 0.15% v/v, about0.20% v/v, about 0.25% v/v, about 0.3% v/v, about 0.35% v/v, about 0.4%v/v, about 0.45% v/v, about 0.50% v/v, about 0.55% v/v, about 0.60% v/v,about 0.65% v/v, about 0.70% v/v, about 0.75% v/v, about 0.80% v/v,about 0.85% v/v, about 0.90% v/v, about 0.95% v/v, about 1.0% v/v, about2.0% v/v, about 3.0% v/v, about 4.0% v/v, or about 5.0% v/v, includingall values and ranges in between.

Preservatives

In some embodiments, the compositions of the disclosure containpreservatives. Non-limiting examples of preservatives include quaternaryammonium preservatives such as polyquaternium-1 and benzalkonium halides(e.g., benzalkonium chloride (“BAC”) and benzalkonium bromide), parabens(e.g., methylparabens and propylparabens), phenoxyethanol, benzylalcohol, chlorobutanol, phenol, sorbic acid and salts thereof,thimerosal, potassium sorbate, or combinations thereof. In someembodiments, paraben is not included in the formulations of thedisclosure.

Thickening Agents

In some embodiments, the compositions of the disclosure containthickening agents. Thickening agents, including thickener or gellingagents, include substances which that can increase the viscosity of acomposition. Thickeners includes those that can increase the viscosityof a composition without substantially modifying the efficacy of theactive ingredient within the composition. Thickeners can also increasethe stability of the compositions of the present invention. In certainaspects of the present invention, thickeners include hydrogenatedpolyisobutene, trihydroxystearin, ammonium acryloyldimethyltaurate/vpcopolymer, or a mixture thereof.

Non-limiting examples of additional thickening agents that can be usedin the context of the present invention include carboxylic acidpolymers, cross-linked polyacrylate polymers, polyacrylamide polymers,polysaccharides, and gums. Examples of carboxylic acid polymers includecross-linked compounds containing one or more monomers derived fromacrylic acid, substituted acrylic acids, and salts and esters of theseacrylic acids and the substituted acrylic acids, wherein thecrosslinking agent contains two or more carbon-carbon double bonds andis derived from a polyhydric alcohol (see U.S. Pat. Nos. 5,087,445;4,509,949; 2,798,053; CTFA International Cosmetic Ingredient Dictionary,Fourth edition, 1991, pp. 12 and 80). Examples of commercially availablecarboxylic acid polymers include carbomers, which are homopolymers ofacrylic acid cross-linked with allyl ethers of sucrose orpentaerythritol (e.g., Carbopol™ 900 series from B. F. Goodrich).

Non-limiting examples of cross-linked polyacrylate polymers includecationic and nonionic polymers. Examples are described in U.S. Pat. Nos.5,100,660; 4,849,484; 4,835,206; 4,628,078; 4,599,379, each of which isincorporated by reference in its entirety herein.

Non-limiting examples of polyacrylamide polymers (including nonionicpolyacrylamide polymers including substituted branched or unbranchedpolymers) include polyacrylamide, iso-paraffin and laureth-7,multi-block copolymers of acrylamides and substituted acrylamides withacrylic acids and substituted acrylic acids.

Non-limiting examples of polysaccharides include cellulose,carboxymethyl hydroxyethylcellulose, cellulose acetate propionatecarboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose,hydroxypropylcellulose, hydroxypropyl methylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulosesulfate, and mixtures thereof. Another example is an alkyl substitutedcellulose where the hydroxy groups of the cellulose polymer ishydroxyalkylated (preferably hydroxy ethylated or hydroxypropylated) toform a hydroxyalkylated cellulose which is then further modified with aC10-C30 straight chain or branched chain alkyl group through an etherlinkage. Typically these polymers are ethers of C10-C30 straight orbranched chain alcohols with hydroxyalkylcelluloses. Other usefulpolysaccharides include scleroglucans comprising a linear chain of (1-3)linked glucose units with a (1-6) linked glucose every three unit.

Non-limiting examples of gums that can be used with the presentinvention include acacia, agar, algin, alginic acid, ammonium alginate,amylopectin, calcium alginate, calcium carrageenan, carnitine,carrageenan, dextrin, gelatin, gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydratedsilica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp,locust bean gum, natto gum, potassium alginate, potassium carrageenan,propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran,sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

Silicone Containing Compounds

In some embodiments, the compositions of the disclosure contain asilicone containing compound. In non-limiting aspects, siliconecontaining compounds include any member of a family of polymericproducts whose molecular backbone is made up of alternating silicon andoxygen atoms with side groups attached to the silicon atoms. By varyingthe —Si—O— chain lengths, side groups, and crosslinking, silicones canbe synthesized into a wide variety of materials. They can vary inconsistency from liquid to gel to solids.

The silicone containing compounds that can be used in the context of thepresent disclosure include those described in this specification orthose known to a person of ordinary skill in the art. Non-limitingexamples include silicone oils (e.g., volatile and non-volatile oils),gels, and solids. In certain aspects, the silicon containing compoundsincludes a silicone oils such as a polyorganosiloxane. Non-limitingexamples of polyorganosiloxanes include dimethicone, cyclomethicone,polysilicone-11, phenyl trimethicone, trimethylsilylamodimethicone,stearoxytrimethylsilane, or mixtures of these and other organosiloxanematerials in any given ratio in order to achieve the desired consistencyand application characteristics depending upon the intended application(e.g., to a particular area such as the skin, hair, or eyes). A“volatile silicone oil” includes a silicone oil have a low heat ofvaporization, i.e. normally less than about 50 cal per gram of siliconeoil. Non-limiting examples of volatile silicone oils include:cyclomethicones such as Dow Corning 344 Fluid, Dow Corning 345 Fluid,Dow Corning 244 Fluid, and Dow Corning 245 Fluid, Volatile Silicon 7207(Union Carbide Corp., Danbury, Conn.); low viscosity dimethicones, i.e.dimethicones having a viscosity of about 50 cst or less (e.g.,dimethicones such as Dow Corning 200-0.5 cst Fluid). The Dow CorningFluids are available from Dow Corning Corporation, Midland, Mich.Cyclomethicone and dimethicone are described in the Third Edition of theCTFA Cosmetic Ingredient Dictionary (incorporated by reference) ascyclic dimethyl polysiloxane compounds and a mixture of fully methylatedlinear siloxane polymers end-blocked with trimethylsiloxy units,respectively. Other non-limiting volatile silicone oils that can be usedin the context of the present disclosure include those available fromGeneral Electric Co., Silicone Products Div., Waterford, N.Y. and SWSSilicones Div. of Stauffer Chemical Co., Adrian, Mich.

Essential Oils

In some embodiments, the compositions of the disclosure containessential oils. Essential oils include oils derived from herbs, flowers,trees, and other plants. Such oils are typically present as tinydroplets between the plant's cells, and can be extracted by severalmethod known to those of skill in the art (e.g., steam distilled,enfleurage (extraction by using fat), maceration, solvent extraction, ormechanical pressing). When these types of oils are exposed to air theytend to evaporate (i.e., a volatile oil). As a result, many essentialoils are colorless, but with age they can oxidize and become darker.Essential oils are insoluble in water and are soluble in alcohol, ether,fixed oils (vegetal), and other organic solvents. Typical physicalcharacteristics found in essential oils include boiling points that varyfrom about 160° C. to 240° C. and densities ranging from about 0.759g/mL to about 1.096 g/mL.

Essential oils typically are named by the plant from which the oil isfound. For example, rose oil or peppermint oil are derived from rose orpeppermint plants, respectively. Non-limiting examples of essential oilsthat can be used in the context of the present invention include sesameoil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sageoil, Spanish rosemary oil, coriander oil, thyme oil, pimento berriesoil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedaroil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil,eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geraniumoil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil,lemon oil, lemongrass oil, lime oil, mandarin oil, marjoram oil, myrrhoil, neroli oil, orange oil, patchouli oil, pepper oil, black pepperoil, petitgrain oil, pine oil, rose otto oil, rosemary oil, sandalwoodoil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, orylang ylang. Other essential oils known to those of skill in the art arealso contemplated as being useful within the context of the presentinvention.

Carrier Oils

In some embodiments, the compositions of the disclosure contain carrieroils. Carrier oils are used to dilute essential oils so they can beapplied to the skin without side effects. Non-limiting examples ofcarrier oils include coconut oil (Cocus nucifera), black cumin seed oil(Nigella sativa), jojoba oil (Simmondsia chinensis), evening primroseoil Oenothera biennis), rose hip oil (Rosa mosqueta), aloe (Aloe vera),and grapeseed oil (Vitus vinifera). In some embodiments, Aloe vera isused as a carrier oil.

Structuring Agents

In some embodiments, the compositions of the disclosure containstructuring agents. Structuring agents, in certain aspects, assist inproviding rheological characteristics, which contribute to thecomposition's stability. In other aspects, structuring agents can alsofunction as an emulsifier or surfactant. Non-limiting examples ofstructuring agents include stearic acid, palmitic acid, stearyl alcohol,cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, thepolyethylene glycol ether of stearyl alcohol having an average of about1 to about 21 ethylene oxide units, the polyethylene glycol ether ofcetyl alcohol having an average of about 1 to about 5 ethylene oxideunits, and mixtures thereof.

Vitamins and Minerals

In some embodiments, the compositions of the disclosure contain one ormore vitamins, minerals, or amino acids. Non-limiting examples ofvitamins include vitamin A, ascorbic acid (vitamin C), vitamin D,vitamin E, vitamin K, thiamine, riboflavin, niacin, pantothenic acid,pyridoxine, biotin, folate, cobalamin, and cyanocobalamin. Non-limitingexamples of minerals that can be included in the compositions of thepresent invention include antimony, barium, beryllium, bismuth, boron,bromine, calcium, carbon, cerium, cesium, chloride, chromium, cobalt,copper, dysprosium, erbium, europium, fluorine, gadolinium, gallium,germanium, gold, hafnium, holmium, indium, iodine, iridium, iron,lantharum, lithium, magnesium, manganese, molybdenum, neodymium, nickel,niobium, osmium, palladium phosphorus, platinum, potassium,paresodymium, rhenium, rhodium, rubidium, ruthenium, samarium, sodium,selenium, silicon, silver, sodium, strontium, sulfur, tantalum,thallium, thorium, tellurium, terbium, thulium, tin, titanium, tungsten,ytterbium, yttrium, zinc, and zirconium. Any soluble salt of theseminerals suitable for inclusion edible products can be used, forexample, calcium carbonate, calcium citrate, calcium malate,calcium-citrate-malate, calcium gluconate, magnesium citrate, magnesiumgluconate, magnesium sulfate, zinc chloride, zinc sulfate, potassiumiodide, and copper sulfate.

In some embodiments, the compositions of the disclosure include aminoacids. Non-limiting examples of amino acids include alanine, glutamicacid, glycine, histidine, isoleucine, leucine, methionine,phenylalanine, serine, threonine, tryptophan, valine, aspartic acid,arginine, asparagine, glutamine, proline, cysteine, and lysine.

In some embodiments, the minerals and amino acids are contained within aproduct, which is incorporated into the compositions of the disclosure.For example, DERMA BOOST™ can be utilized in the compositions of thedisclosure.

In some embodiments, the compositions of the disclosure containretinoids. Retinoids have shown promise in the treatment of aging,burns, scaling, and dermatitis. Non-limiting examples of retinoidsinclude retinol, tretinoin, adapalene, tazarotene, alitretinoin,isortetinoin, retinyl palmitate, retinaldehyde, and bexarotene.

Pharmaceutical Ingredients

In some embodiments, the compositions of the disclosure containpharmaceutical ingredients. Non-limiting examples of pharmaceuticalactive agents include anti-acne agents, agents used to treat rosacea,analgesics, anesthetics, anorectals, antihistamines, anti-inflammatoryagents including non-steroidal anti-inflammatory drugs, antibiotics,antifungals, antivirals, antimicrobials, anti-cancer actives,scabicides, pediculicides, antineoplastics, antiperspirants,antipruritics, antipsoriatic agents, antiseborrheic agents, biologicallyactive proteins and peptides, burn treatment agents, cauterizing agents,depigmenting agents, depilatories, diaper rash treatment agents,enzymes, hair growth stimulants, hair growth retardants includingdifluoromethylonithine (DFMO) and its salts and analogs, hemostatics,kerotolytics, canker sore treatment agents, cold sore treatment agents,dental and periodontal treatment agents, photosensitizing actives, skinprotectant/barrier agents, steroids including hormones andcorticosteroids, sunburn treatment agents, sunscreens, transdermalactives, nasal actives, vaginal actives, wart treatment agents, woundtreatment agents, and wound healing agents.

In some embodiments, the pharmaceutical ingredient is a steroid.Non-limiting examples of steroids include dexamethasone, dexamethasoneacetate, dexamethasone sodium phosphate, cortisone, cortisone acetate,hydrocortisone, hydrocortisone acetate, hydrocortisone cypionate, sodiumhydrocortisone phosphate, prednisol hydrochloroneone acetate, prednisolacetate Prednisolone, Prednisolone Sodium Phosphate, PrednisoloneTebutate, Prednisolone Pivalate, Triamcinolone, Triamcinolone Acetonide,Triamcinolone Hexacetonide, Triamcinolone Diacetate, MethylprednisoloneMethylprednisolone Acetate, Sodium Methodotassium Sodium Methionate,Sodium Methionate Diploate betamethasone, betamethasone, disodiumphosphate of vetamethasone, sodium phosphate of vetamethasone,betamethasone acetate, disodium phosphate of betamethasone,chloroprednisone acetate, corticosterone, deoxycorticosterone,deoxycorticosterone acetate, deoxymethyrostaone deoxyketol ester,fludrocortisone, fludrocortisone acetate, dichlorisone acetate,fluorohydrocortisone, fluorometolone, fluprednisolone, parametasona,parametasona acetate, androsterone, fluoxymesterone, aldosterone,methandrostenolone, methyrostenedione, methyldostentaone testosterone,testosterone testosterone, testosterone equonates testosterone,estradiol benzoate, estradiol dipropionate, estriol, estrone, estronebenzoate, acetoxypregnenolone, anagestone acetate, chlormadinoneacetate, flurogestone acetate, hydroxymethylprogesterone,hydroxymethylprogesterone acetate, hydroxyprogesterone,hydroxyprogesterone hydroxyprogesterone, hydroxyprogesterone acetate,normethisterone, pregnenolone, progesterone, ethinyl estradiol,mestranol, dimethisterone, etisterone, ethinodiol diacetate,norethindrone, norethindrone acetate, norethisterone, fluocinoloneacetonide, flurandrenolone, succinate hydrocortisone succinate,methylprednisolone sodium, prednisolone sodium phosphate, triamcinoloneacetonide, sodium hydroxydione, spironolactone, oxandrolone,oxymetholone, prometholone, testosterone cypionate, testosteronephenylacetate, estradiol cypionate and noretynodrel.

Other Cosmetic Compositions

In some embodiments, the compositions of the disclosure contain othercosmetic compositions. In some embodiments, BEYOND FLAWLESS™ Second Skinis incorporated into the compositions or products of the disclosure.BEYOND FLAWLESS™ Second Skin contains graphene, stabilized vitamin C,peptides and extracts, which provide anti-aging skin care benefits.

In some embodiments, the compositions of the disclosure contain tonersor texturizers.

In some embodiments, the cosmetics of the disclosure contain salicylicacid.

Antioxidants

In some embodiments, the compositions of the disclosure containantioxidants. Antioxidants are substances that inhibit oxidation.Non-limiting examples of antioxidants that can be used with thecompositions of the present invention include acetyl cysteine, ascorbicacid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanolpectinate, ascorbyl palmitate, ascorbyl stearate, butated hydroxyanisole(BHA), butylated hydroxytoluene (BHT), t-butyl hydroquinone, cysteine,cysteine HCl, diamylhydroquinone, di-t-butylhydroquinone, dicetylthiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbylsulfate, distearyl thiodipropionate, ditridecyl thiodipropionate,dodecyl gallate, erythorbic acid, esters of ascorbic acid, ethylferulate, ferulic acid, gallic acid esters, hydroquinone, isooctylthioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbylphosphate, methylsilanol ascorbate, natural botanical anti-oxidants suchas green tea or grape seed extracts, nordihydroguaiaretic acid, octylgallate, phenylthioglycolic acid, potassium ascorbyl tocopherylphosphate, potassium sulfite, propyl gallate, quinones, rosmarinic acid,sodium ascorbate, sodium bisulfate, sodium erythorbate, sodiummetabisulfite, sodium sulfite, superoxide dismutase, sodiumthioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide,thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylicacid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18,tocophereth-50, tocopherol, tocophersolan, tocopheryl acetate,tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate, andtris(nonylphenyl)phosphite.

Ingredients which May be Avoided

In some embodiments, one or more of the following ingredients is notincluded in the compositions of the disclosure. Non-limiting examples ofingredients that are not included are parabens, sulfates, alcohols,dyes, and fragrances. In some embodiments, the compositions of thedisclosure do not include parabens. In some embodiments, thecompositions of the disclosure do not include sulfates. In someembodiments, the compositions of the disclosure do not include alcohols.In some embodiments, the compositions of the disclosure do not includedyes. In some embodiments, the compositions of the disclosure do notinclude fragrances.

Cosmetic Vehicles

In some embodiments, the active ingredients and additional ingredientsare mixed with a cosmetic vehicle. A cosmetic vehicle facilitates thedelivery of an ingredient of the skin composition to the skin. In someembodiments, a cosmetic vehicle is selected from the group consisting ofliposome, nanosome, emulsion, microemulsion, nanocapsules, solid lipidnanoparticles, and nanocrystals.

In some embodiments, the cosmetic vehicle is a liposome. Liposomes arevesicular structures, which have an aqueous core enclosed by a lipidbilayer. In some embodiments, liposomes contain phospholipids or fattyacids. In some embodiments, liposomes range in size from 15 nm indiameter to several micrometers in diameter. In some embodiments,liposomes exhibit a unilamellar structure or a multilamellar structure.Liposomes facilitate the continuous supply of active ingredients oradditional ingredients to cells over a sustained period of time.

In some embodiments, the cosmetic vehicle is a nanosome. Nanosomes areliposomes with a particle size of between about 20 nm to about 600 nm.In some embodiments, the nanosomes of the disclosure have a particlesize of about 20 nm, or about 30 nm, or about 40 nm, or about 50 nm, orabout 60 nm, or about 70 nm, or about 80 nm, or about 90 nm, or about100 nm, or about 200 nm, or about 300 nm, or about 400 nm, or about 500nm, or about 600 nm. A representative methods for preparing liposomes isfound in International Publication No. 2008/010241 (published Jan. 24,2008), which is incorporated by reference herein, in its entirety.Example 1 shows a method of preparing liposomes.

In some embodiments, the cosmetic vehicle is an emulsion. An emulsion isa dispersed system containing at least two immiscible liquid phases, oneof which is dispersed in the form of small droplets throughout theother, and an emulsifying agent to improve the stability of the system.Non-limiting examples of emulsifying agents include esters of glycerin,esters of propylene glycol, fatty acid esters of polyethylene glycol,fatty acid esters of polypropylene glycol, esters of sorbitol, esters ofsorbitan anhydrides, carboxylic acid copolymers, esters and ethers ofglucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates,polyoxyethylene fatty ether phosphates, fatty acid amides, acyllactylates, soaps, TEA stearate, DEA oleth-3 phosphate, polyethyleneglycol 20 sorbitan monolaurate (polysorbate 20), polyethylene glycol 5soya sterol, steareth-2, steareth-20, steareth-21, ceteareth-20,cetearyl glucoside, cetearyl alcohol, C12-13 pareth-3, PPG-2 methylglucose ether distearate, PPG-5-ceteth-20, bis-PEG/PPG-20/20dimethicone, ceteth-10, polysorbate 80, cetyl phosphate, potassium cetylphosphate, diethanolamine cetyl phosphate, polysorbate 60, glycerylstearate, PEG-100 stearate, arachidyl alcohol, arachidyl glucoside, andmixtures thereof.

In some embodiments, emulsions are classified according to the dropletsize of the liquids present in the emulsions. Nanoemulsions are systemscontaining droplets with particle sizes from 10 to 1000 nm.Microemulsions are systems containing droplets with particle sizes fromabout 5 nm to about 100 nm. McClements, which is incorporated byreference herein in its entirety, discusses characteristics ofnanoemulsions and microemulsions (McClements. 2012, Soft Matter8(6):1719-1729). Macroemulsions are systems containing droplets withaverage particle sizes between about 10 μm and about 1000 μm. In someembodiments, the emulsion is selected from the group consisting ofwater-in-oil, oil-in-water, silicone-in-water, and water-in-silicone. Insome embodiments, the emulsion is a multiple emulsion system, such aswater-in-oil-in-water, oil-in-water-in-oil, andoil-in-water-in-silicone. The name of the emulsion indicates theidentities of the immiscible phases.

In some embodiments, “oil” signifies the oil phase of an emulsion.Non-limiting examples of oils which may be utilized within the oil phaseinclude hydrocarbon oils of animal origin and hydrocarbon oils ofvegetable origin. Non-limiting examples of hydrocarbon oils of vegetableorigin include liquid triglycerides of fatty acids comprising 4 to 10carbon atoms such as triglycerides of heptanoic or octanoic acids oralso, for example, sunflower, corn, and soy, pumpkin, grape seeds,sesame, hazelnut, apricot, macadamia, arara, sunflower, castor, avocado,and triglycerides of caprylic/capric acids. In some embodiments, the oilphase of the emulsion contains from about 10% w/w to about 90% w/w. Insome embodiments, the oil phase of the emulsion is about 5% w/w, orabout 10% w/w, or about 15% w/w, or about 20% w/w, or about 25% w/w, orabout 30% w/w, or about 35% w/w, or about 40% w/w, or about 45% w/w, orabout 50% w/w, or about 55% w/w, or about 60% w/w, or about 65% w/w, orabout 70% w/w, or about 75% w/w, or about 80% w/w, or about 85% w/w, orabout 90% w/w.

In some embodiments, “water” signifies the water phase of an emulsion.In some embodiments, the water phase of the emulsion contains from about10% w/w to about 90% w/w. In some embodiments, the water phase of theemulsion is about 5% w/w, or about 10% w/w, or about 15% w/w, or about20% w/w, or about 25% w/w, or about 30% w/w, or about 35% w/w, or about40% w/w, or about 45% w/w, or about 50% w/w, or about 55% w/w, or about60% w/w, or about 65% w/w, or about 70% w/w, or about 75% w/w, or about80% w/w, or about 85% w/w, or about 90% w/w.

In some embodiments, the cosmetic vehicle of the compositions of thedisclosure is an oil-in-water emulsion. In some embodiments, thecosmetic vehicle comprises 55% w/w to 70% w/w water and furthercomprises glyceryl stearate, pentylene glycol, ethylhexyl isononanoate,cetyl alcohol, butyrosperum parkii (shea) butter, Zea mays (cor) germoil, cetyl phosphate, cetearyl alcohol, and ceteareth-33. In someembodiments, the oil-in-water emulsion comprises 20% w/w to 40% w/wwater and further comprises phospholipids, glycerin, and caprylic/caprictriglycerides. In some embodiments, the oil-in-water emulsion comprises3% v/v phospholipids, 54% v/v glycerin, and 10% v/v caprylic/caprictriglycerides. An exemplary oil-in-water emulsion that may be used inthe compositions of the disclosure is shown in Table 1.

TABLE 1 Exemplary oil-in-water emulsion Component Weight percent (% v/v)Phospholipids 0-5 Caprylic/capric triglyceride  5-15 Glycerin 40-60

In some embodiments, the cosmetic vehicle is mixed with the otheringredients (i.e. active ingredients and additional ingredients) at aratio of cosmetic vehicle to other ingredients of about 9:1 w/w, about8:2 w/w, about 7:3 w/w, about 6:4 w/w, about 5:5 w/w, about 4:6 w/w,about 3:7 w/w, about 2:8 w/w, or about 1:9 w/w.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% w/w phospholipids (lecithin), about 54% w/w glycerin, about 10%w/w caprylic/capric triglyceride, about 1% w/w CBD, about 2% w/w roseoil, about 1% w/w humectant, about 0.1% w/w tocopherol, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% w/w phospholipids (lecithin), about 54% w/w glycerin, about 10%w/w caprylic/capric triglyceride, about 1% w/w CBD, about 2% w/w roseoil, about 1% w/w humectant, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% v/v phospholipids (lecithin), about 54% v/v glycerin, about 10%v/v caprylic/capric triglyceride, about 1% v/v CBD, about 2% v/v roseoil, about 1% v/v humectant, about 0.1% v/v tocopherol, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% v/v phospholipids (lecithin), about 54% v/v glycerin, about 10%v/v caprylic/capric triglyceride, about 1% v/v CBD, about 2% v/v roseoil, about 1% v/v humectant, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% v/v phospholipids (lecithin), about 54% v/v glycerin, about 10%v/v caprylic/capric triglyceride, about 1% w/v CBD, about 2% v/v roseoil, about 1% v/v humectant, about 0.1% v/v tocopherol, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprisesabout 3% v/v phospholipids (lecithin), about 54% v/v glycerin, about 10%v/v caprylic/capric triglyceride, about 1% w/v CBD, about 2% v/v roseoil, about 1% v/v humectant, and water.

In some embodiments, the formulation containing rose oil, cannabidiol, ahumectant, additional ingredients, and a cosmetic vehicle comprises aformulation selected from any one of Formulations A-P, as described inTables 2-5.

Properties and Stability of Formulation Containing Rose Oil,Cannabidiol, and Humectant

In some embodiments, the compositions of the disclosure are stable for12 or more months. In some embodiments, the compositions of thedisclosure are stable for 12 months, or 13 months, or 14 months, or 15months, or 16 months, or 17 months, or 18 months, or 19 months, or 20months, or 21 months, or 22 months, or 23 months, or 24 months. In someembodiments, the compositions of the disclosure are stable for at least12 months. In some embodiments, the compositions of the disclosure arestable at 25° C. in a closed container in a dark space.

In some embodiments, the compositions of the disclosure are liquids. Insome embodiments, the compositions of the disclosure aregreen-yellowish.

In some embodiments, the compositions of the disclosure are stable fromabout pH 4.5 to about pH 7.5.

In some embodiments, the compositions of the disclosure have sensoryfeatures selected from the group consisting of light, hydrating,soothing, healing, and repairing.

In some embodiments, the compositions of the disclosure have physicalfeatures selected from the group consisting of smooth, silky, whippedcream, rich texture, easily spread onto the skin, and easily absorbed.

In some embodiments, the compositions of the disclosure have a pleasantsmell.

Products Containing Rose Oil, Cannabidiol, and Humectant Formulation

In some embodiments, the compositions of the present disclosure is usedin many cosmetic products. In some embodiments, the compositions of thepresent disclosure are incorporated into cosmetic products oralternative formulations at up to about 5% w/w. In some embodiments, thecompositions are incorporated into cosmetic products or alternativeformulations at about 0.1% w/w, about 0.2% w/w, about 0.3% w/w, about0.4% w/w, about 0.5% w/w, about 0.6% w/w, about 0.7% w/w, about 0.8%w/w, about 0.9% w/w, about 1.0% w/w, about 1.1% w/w, about 1.2% w/w,about 1.3% w/w, about 1.4% w/w, about 1.5% w/w, about 1.6% w/w, about1.7% w/w, about 1.8% w/w, about 1.9% w/w, about 2.0% w/w, about 2.5%w/w, about 3.0% w/w, about 3.5% w/w, about 4.0% w/w, about 4.5% w/w, orabout 5.0% w/w, including all values and ranges in between. In someembodiments, the compositions of the present disclosure are incorporatedinto cosmetic products or alternative formulations at between about 1%and about 2%.

Non-limiting examples of cosmetic products include, but are not limitedto, lip sticks, lip balms, lip glosses, serums, face serums, sunscreenproducts, sunless skin tanning products, hair products, finger nailproducts, moisturizing creams, skin benefit creams and lotions,softeners, day lotions, gels, ointments, foundations, night creams, eyecreams, face creams, cleansers, face masks, toners, masks, sheet masks,or other known cosmetic products or applications.

In some embodiments, the compositions of the present disclosure areincorporated into serums. Serums are skin care products that aredesigned to deliver high concentrations of active ingredients to theskin. In some embodiments, serums are clear, gel-based, or liquid. Insome embodiments, serums are more hydrating than creams. In someembodiments, the compositions of the disclosure are incorporated into awater-based serum. In some embodiments, the compositions of thedisclosure are incorporated into an oil-based serum. In someembodiments, serums are applied to the top of a face cream or lotion. Insome embodiments, serums are applied directly to the skin. U.S.Publication No. 2004/0191330 (published Sep. 30, 2004) which describeshow to apply a serum is incorporated by reference herein in itsentirety.

In some embodiments, the compositions of the present disclosure areincorporated into a mask selected from the group consisting of sheetmasks, clay masks, cream masks, peel-off masks, gel masks, charcoalmasks, and sleep masks.

In some embodiments, the compositions of the disclosure are incorporatedinto charcoal masks or clay masks. In some embodiments, charcoal masksand clay masks draw out impurities form a person's skin. In someembodiments, charcoal masks and clay masks are used to brighten theskin.

In some embodiments, the compositions of the disclosure are incorporatedinto gel masks, which have a cooling sensation. In some embodiments,cream masks are applied to dry skin. In some embodiments, clay andcharcoal masks are applied to oily skin.

In some embodiments, the compositions of the present disclosure areincorporated in sheet masks. In some embodiments, a sheet mask containsa fabric soaked in a serum containing the composition of the disclosure.Non-limiting examples of fabrics used for sheet masks include cotton,microfiber, cupra, tencel, hydrogels, bio-cellulose, foil, and charcoal.In some embodiments, a sheet mask is applied to skin. In someembodiments, the sheet mask is applied to a person's face. In someembodiments, a sheet mask is applied to a person's eyes, nose, lips,décolletage, hair, or feet.

In some embodiments, a mask containing the compositions of the presentdisclosure is washed off with water. In some embodiments, a peel-offmask containing the compositions of the present disclosure is peeledoff.

In some embodiments, the compositions of the present disclosure areincorporated into eye creams. In some embodiments, eye creams areapplied to the delicate skin around the eye. In some embodiments, eyecreams are applied around the eyes to reduce puffiness and dark circles.In some embodiments, eye creams are applied to moisturize the area ofskin around the eyes. In some embodiments, eye creams are applied tofirm the skin around the eyes. In some embodiments, application of eyecreams around the eyes decreases fine lines and wrinkles. U.S.Publication No. 2004/0191330 (published Sep. 30, 2004) which describeshow to apply an eye cream is incorporated by reference herein in itsentirety.

In some embodiments, the compositions of the present disclosure areincorporated into face creams. In some embodiments, face creams areapplied to a person's face. In some embodiments, face creams are used tomoisturize a person's face. In some embodiments, face creams are appliedat night. In some embodiments, face creams are applied in the morning.

In certain embodiments, products containing rose oil, cannabidiol, andhumectants are placed in a container. The container can be a bottle,dispenser, or package. The container can dispense a pre-determinedamount of the composition. In certain aspects, the composition isdispensed in a spray, mist, dollop, or liquid. In some embodiments, thecomposition is placed in a 15 ml glass canister. In some embodiments,the composition is placed in a 30 mL glass canister. The container caninclude indicia on its surface. The indicia can be a word, anabbreviation, a picture, or a symbol.

Methods of Using the Compositions of the Disclosure

In some embodiments, the compositions of the disclosure are used forregulating a skin condition. In some embodiments, the compositions areapplied topically to a subject's skin. In some embodiments, the subjectis a mammal. In some embodiments, the subject is an animal or a human.Non-limiting examples of animals include dogs, cats, wolves, bears,tigers, lions, monkeys, guinea pigs, ferrets, pigs, hamsters, andrabbits.

In some embodiments, the compositions are applied to the skin. In someembodiments, the compositions of the disclosure are applied to theepidermis. In some embodiments, the compositions of the disclosurepenetrate the dermis. In some embodiments, the compositions of thedisclosure penetrate the hypodermis. In some embodiments, thecompositions of the disclosure are applied to the face, scalp, hands,neck, décolleté, scalp, paw, hand, palm, arm, leg, foot, sole, chest,breast, back, abdomen, buttock, vulva, eyelid, nipples, penis, scrotum,anus, or any other skin areas of a subject. In some embodiments, thecompositions of the disclosure are applied to the lips. In someembodiments, the composition is applied to the whole body.

In some embodiments, the compositions of the disclosure are applied tothe hair. The compositions may serve as a shampoo, conditioner,detangler, or a leave-in conditioner.

In some embodiments, the compositions are applied as a product of thedisclosure, described above. In some embodiments, the compositions areapplied for an extended period for an aesthetic, prophylactic, ortherapeutic benefit (i.e. a “leave-on” composition). In someembodiments, the leave-on composition is left on the skin for a periodof at least 1 minute, or at least 2 minutes, or at least 3 minutes, orat least 4 minutes, or at least 5 minutes, or at least 6 minutes, or atleast 7 minutes, or at least 8 minutes, or at least 9 minutes, or atleast 10 minutes, or at least 15 minutes, or at least 20 minutes, or atleast 25 minutes, or at least 30 minutes, or at least 45 minutes, or atleast 1 hour, or at least 12 hours, or up to 24 hours, including allranges in between.

In some embodiments, the compositions are applied one or more times perday. In some embodiments, the compositions are applied once per day. Insome embodiments, the compositions are applied twice a day, or threetimes a day, or four time a day, or more. In some embodiments, thecompositions are applied every other day, or every third day, or everyfourth day, or every fifth day, or every sixth day, or once per week.

In some embodiments, the compositions of the disclosure are used toregulate a skin condition. In some embodiments, the compositions areused to regulate visible, tactile, or visible and tactilediscontinuities in the skin. In some embodiments, the discontinuitiesare associated with aging. In some embodiments, the discontinuities areassociated with puberty. Non-limiting examples of discontinuitiesinclude acne, fine lines, wrinkles, dark spots, burns, stretch marks,and enlarged pores. In some embodiments, the compositions of thedisclosure are used to treat psoriasis, dermatitis, sunburn, androsacea. In some embodiments, the compositions of the disclosure arehave properties selected from the group consisting of anti-bacterial,anti-inflammatory, and anti-oxidants. In some embodiments, thecompositions of the disclosure are anti-inflammatory. In someembodiments, the compositions of the disclosure are anti-oxidants. Insome embodiments, the compositions of the disclosure are anti-bacterial.

In some embodiments, the compositions of the disclosure are applied forhydration of the skin. In some embodiments, the compositions of thedisclosure are used as a sunblock. In some embodiments, the compositionsof the disclosure are utilized to prevent photo-aging. In someembodiments, the compositions of the disclosure are utilized to repairskin cells. In some embodiments, the compositions of the disclosure areused to protect skin from external factors. In some embodiments, thecompositions of the disclosure are used for eye care. In someembodiments, the compositions of the disclosure are used to reduce finelines or wrinkles near the eyes.

In some embodiments, when a subject is treated with the compositions ofthe disclosure, the subject exhibits a reduction in acne compared topre-treatment of about 5%, or about 10%, or about 15%, or about 20%, orabout 25%, or about 30%, or about 35%, or about 40%, or about 45%, orabout 50%, or about 55%, or about 60%, or about 65%, or about 70%, orabout 75%, or about 80%, or about 85%, or about 90%, or about 95%, ormore.

In some embodiments, when a subject is treated with the compositions ofthe disclosure, the subject exhibits a reduction in fine lines comparedto pre-treatment of about 5%, or about 10%, or about 15%, or about 20%,or about 25%, or about 30%, or about 35%, or about 40%, or about 45%, orabout 50%, or about 55%, or about 60%, or about 65%, or about 70%, orabout 75%, or about 80%, or about 85%, or about 90%, or about 95%, ormore.

In some embodiments, when a subject is treated with the compositions ofthe disclosure, the subject exhibits a reduction in wrinkles compared topre-treatment of about 5%, or about 10%, or about 15%, or about 20%, orabout 25%, or about 30%, or about 35%, or about 40%, or about 45%, orabout 50%, or about 55%, or about 60%, or about 65%, or about 70%, orabout 75%, or about 80%, or about 85%, or about 90%, or about 95%, ormore.

In some embodiments, when a subject is treated with the compositions ofthe disclosure, the subject exhibits a reduction in dark spots comparedto pre-treatment of about 5%, or about 10%, or about 15%, or about 20%,or about 25%, or about 30%, or about 35%, or about 40%, or about 45%, orabout 50%, or about 55%, or about 60%, or about 65%, or about 70%, orabout 75%, or about 80%, or about 85%, or about 90%, or about 95%, ormore.

In some embodiments, when a subject is treated with the compositions ofthe disclosure, the subject exhibits a reduction in stretch markscompared to pre-treatment of about 5%, or about 10%, or about 15%, orabout 20%, or about 25%, or about 30%, or about 35%, or about 40%, orabout 45%, or about 50%, or about 55%, or about 60%, or about 65%, orabout 70%, or about 75%, or about 80%, or about 85%, or about 90%, orabout 95%, or more.

In some embodiments, when a subject with a wound is treated with thecompositions of the disclosure, the subject exhibits healing of thewound. In some embodiments, the compositions of the disclosure causemigration of skin cells or skin stem cells to the wound.

In some embodiments, the compositions of the disclosure areanti-inflammatory. In some embodiments, the compositions of thedisclosure inhibit PGE₂ release by keratinocytes. In some embodiments,the compositions of the disclosure reduce secretion of an inflammatorymarker. In some embodiments, the disclosure inhibit release of one ormore chemokines, including but not limited to IL-8. In some embodiments,the disclosure inhibit or augment release of one or more cytokines.

In some embodiments, regulation of skin condition can be visualized,analyzed, measured and quantified using many techniques known by thespecialist in cosmetic or skin rejuvenation treatments.

In some embodiments, decrease of fine lines, wrinkles, skin folds, andof skin roughness can be quantified either directly on the personcontact-free using fringe projection (FOITS=Fast Optical In vivoTopometry System; Dermatop™ or Primos™ system), or by silicon replicasof the skin area which are then analyzed by the technique called “dropshadows” or by a FOITS system, or by a Canfield VISIA™ device. Changesin volume and shape of the face can be quantified using a reliefobtaining system without contact using a fringe projection FOITS system.Alteration of the skin barrier can be quantified by measuringtransepidermal water loss (TEWL) using a Tewameter™, a Vapometer™, aDermalab™, and/or an Aquaflux™ device. Loss of firmness and/orelasticity and/or tone and fatigue of the skin can be quantified using aCutometer™, a Reviscometer™, an Aeroflexmeter™, a Dynaskin™, aBallistometer™, a Twistometer™ and/or a Dermalab™ device. Dullcomplexion, loss of uniformity of skin tone, pigmentation changes (hypoand hyper pigmentation), local reddening, loss of clarity and brightnessof the complexion, pigmentation spots, rosacea, dark circles aredirectly measurable using a Mexameter™, a Chromameter™, a Colormeter™, aCanfield VISIA™, a Canfield VISIA-CR™, a SIAscope™, a Goniolux™ or aconfocal laser microscope device, and/or by specific color analysis onphoto (enabled by the technique of photographing in polarized crossedand parallel light). The number and size of facial pores can bequantified by the silicon replica technology described above, or byspecific analysis on photo (enabled by using a video microscope or amacroscopic photographing system). Atrophy and thinning of the skin,epidermis, dermis, or hypodermis (e.g., in case of studying slimmingagents) is measurable by measuring TEWL (e.g., in case of studying theepidermis), or by an ultrasound echographic device, and/or a confocallaser microscope device. Density of skin fibers can be quantified byultrasound and then by image analysis. Cellulite is quantified eitherdirectly by a relief obtaining system without contact using fringeprojection (FOITS) or indirectly by measuring the length of thedermo-hypodermal junction by an ultrasound echographic device. Stretchmarks are either directly quantified using a relief obtaining systemwithout contact using fringe projection (FOITS) or by the siliconreplica technology. Skin softness is directly measurable by techniquesof friction study as with a frictiometer device or indirectly by thesilicon replica technology. Changes in collagen, extracellular matrixcomponents, and/or in connective tissue fibers may be quantified byhistology, confocal laser microscopy, UV spectroscopy, SIAscopie, and/orby multiphoton spectroscopy. All changes visible to the eye (includingbut not limited to fine lines, wrinkles, folds, texture, sagging, lossof elasticity color, tone, pigmentation, redness) can be quantified indirect or on photography, by a trained judge person or not, with orwithout visual scoring system (e.g., using a 4-point severity scale).

EXAMPLES Example 1. Preparation of Nanosomes Containing Rose Oil in theForm of an Extract of Rhododendron ferrugineum (e.g. AlpineRoseActive™),Cannabidiol, and Glycoin

Nanosomes containing rose oil, cannabidiol, and a humectant wereprepared.

Nanosomes were prepared by mixing phospholipids, glycerin, andcaprylic/capric triglycerides. The resultant solution was homogenizedwith a microfluidizer at 1200 bar. The particle size of the liposomeswas analyzed using a photon correlation spectrometer. The averageparticle size of the liposomes was 90±50 nm.

The nanosomes were mixed at a 1:1 w/w ratio with an extract fromRhododendron ferrugineum, CBD, and glyceryl glucoside to form nanosomesencompassing the stem cell extract, CBD, and glyceryl glucoside. Table 2shows the concentrations of the components in the resultantcompositions.

TABLE 2 Exemplary Composition containing Rhododendron ferrugineum, CBD,and glycoin Formulation Formulation Formulation Formulation Component AB C D Phospholipids 3% v/v 3% v/v 3% v/v 3% v/v Glycerin 54% v/v 54% v/v54% v/v 54% v/v Caprylic/capric 10% v/v 10% v/v 10% v/v 10% v/vtriglyceride cannabidiol 1% w/v 1% w/v 1% v/v 1% v/v extract from 2% v/v2% v/v 2% v/v 2% v/v Rhododendron ferrugineum Glyceryl 1% v/v 1% v/v 1%v/v 1% v/v glucoside tocopherol 0.1% v/v 0.1% v/v

Example 2. Preparation of Nanosomes Containing Rose Oil in the Form ofan Extract of Rosa gallica Linne (e.g. Rose Absolute Egyptian Rose),Cannabidiol, and Glycoin

Nanosomes containing rose oil, cannabidiol, and a humectant wereprepared.

Nanosomes were prepared by mixing phospholipids, glycerin, andcaprylic/capric triglycerides. The resultant solution was homogenizedwith a microfluidizer at 1200 bar. The particle size of the liposomeswas analyzed using a photon correlation spectrometer. The averageparticle size of the liposomes was 90±50 nm.

The nanosomes were mixed at a 1:1 w/w ratio with an extract from Rosagallica Linne, CBD, and glyceryl glucoside to form nanosomesencompassing the stem cell extract, CBD, and glyceryl glucoside. Table 3shows the concentrations of the components in the resultant composition.

TABLE 3 Exemplary Composition containing Rosa gallica Linne extract,CBD, and glycoin Formulation Formulation Formulation FormulationComponent E F G H Phospholipids 3% v/v 3% v/v 3% v/v 3% v/v Glycerin 54%v/v 54% v/v 54% v/v 54% v/v Caprylic/capric 10% v/v 10% v/v 10% v/v 10%v/v triglyceride cannabidiol 1% w/v 1% w/v 1% v/v 1% v/v extract from 2%v/v 2% v/v 2% v/v 2% v/v Rosa gallica Linne Glyceryl 1% v/v 1% v/v 1%v/v 1% v/v glucoside tocopherol 0.1% v/v 0.1% v/v

Example 3. Preparation of Nanosomes Containing Rose Oil in the Form ofan Extract of Rhododendron ferrugineum (e.g. AlpineRoseActive™),Cannabidiol, and Hyaluronic Acid

Nanosomes containing rose oil, cannabidiol, and a humectant wereprepared.

Nanosomes were prepared by mixing phospholipids, glycerin, andcaprylic/capric triglycerides. The resultant solution was homogenizedwith a microfluidizer at 1200 bar. The particle size of the liposomeswas analyzed using a photon correlation spectrometer. The averageparticle size of the liposomes was 90±50 nm.

The nanosomes were mixed at a 1:1 w/w ratio with an extract fromRhododendron ferrugineum, CBD, and hyaluronic acid to form nanosomesencompassing the stem cell extract, CBD, and hyaluronic acid. Table 4shows the concentrations of the components in the resultant composition.

TABLE 4 Exemplary Compositions containing Rhododendron ferrugineum, CBD,and hyaluronic acid Formulation Formulation Formulation FormulationComponent I J K L Phospholipids 3% v/v 3% v/v 3% v/v 3% v/v Glycerin 54%v/v 54% v/v 54% v/v 54% v/v Caprylic/capric 10% v/v 10% v/v 10% v/v 10%v/v triglyceride cannabidiol 1% w/v 1% w/v 1% v/v 1% v/v extract from 2%v/v 2% v/v 2% v/v 2% v/v Rhododendron ferrugineum hyaluronic 1% v/v 1%v/v 1% v/v 1% v/v acid tocopherol 0.1% v/v 0.1% v/v

Example 4. Preparation of Nanosomes Containing Rose Oil in the Form ofan Extract of Rosa gallica Linne (e.g. Rose Absolute Egyptian Rose),Cannabidiol, and Hyaluronic Acid

Nanosomes containing rose oil, cannabidiol, and a humectant wereprepared.

Nanosomes were prepared by mixing phospholipids, glycerin, andcaprylic/capric triglycerides. The resultant solution was homogenizedwith a microfluidizer at 1200 bar. The particle size of the liposomeswas analyzed using a photon correlation spectrometer. The averageparticle size of the liposomes was 90±50 nm.

The nanosomes were mixed at a 1:1 w/w ratio with an extract from Rosagallica Linne, CBD, and hyaluronic acid to form nanosomes encompassingthe stem cell extract, CBD, and hyaluronic acid. Table 5 shows theconcentrations of the components in the resultant compositions.

TABLE 5 Exemplary Compositions containing Rosa gallica Linne extract,CBD, and glycoin Formulation Formulation Formulation FormulationComponent M N O P Phospholipids 3% v/v 3% v/v 3% v/v 3% v/v Glycerin 54%v/v 54% v/v 54% v/v 54% v/v Caprylic/capric 10% v/v 10% v/v 10% v/v 10%v/v triglyceride cannabidiol 1% w/v 1% w/v 1% v/v 1% v/v extract from 2%v/v 2% v/v 2% v/v 2% v/v Rosa gallica Linne hyaluronic 1% v/v 1% v/v 1%v/v 1% v/v acid tocopherol 0.1% v/v 0.1% v/v

Example 5. Method of Treating Acne

The ability of the nanosomes of Examples 1-4 to treat acne will bemeasured. As negative controls, nanosomes which lack one or more of theactive ingredients will be utilized (e.g. nanosomes which contain roseoil and a humectant but not CBD, nanosomes which contain a humectant andCBD but not rose oil). The nanosomes will be incorporated into a lotionand applied to a subject with acne's face. Photographs before treatmentand every day after treatment will be used to determine the efficacy ofthe nanosomes for treating acne.

Example 6. Method of Reducing Wrinkles

The ability of the nanosomes of Examples 1-4 to reduce wrinkles will bemeasured. As negative controls, nanosomes which lack one or more of theactive ingredients (e.g. nanosomes which contain rose oil and ahumectant but not CBD, nanosomes which contain a humectant and CBD butnot rose oil) will be utilized. The nanosomes will be incorporated intoa lotion and applied to a subject with wrinkle's face. Photographsbefore treatment and every day after treatment will be used to determinethe efficacy of the nanosomes for reducing wrinkles.

Example 7. Cytotoxicity of Composition Containing Rose Oil, a Humectant,and CBD

The cytotoxicity of S-863d and S-863g on normal human epidermalkeratinocytes (NHEK) was evaluated.

Materials: NHEK cells were used at the third passage and cultured at 37°C. in the presence of 5% CO₂. The NHEK cells were grown in keratinocyteserum free media supplemented with gentamycin (25 μg/mL). S-863dcontained 3% v/v phospholipids, 54% v/v glycerin, 10% v/vcaprylic/capric triglyceride, 1% w/v cannabidiol, 2% v/vAlpineRoseActive™, 1% v/v glycoin, 0.1% v/v tocopherol, and water (ad100%). The particle size (zAve) of S-863d was 90±50 nm, and the pH ofS-863d was between 4.5 and 7.5. The total germ count of S-863d was <100CFU/g. S-863d was stored at 4° C. in a dark space in a closed container.S-863g (negative control) contained 1% CBD in DMSO. S-863d was evaluatedat 0.004%, 0.02%, and 0.1%. S-863g was evaluated at 0.00044%, 0.0013%,and 0.004%.

Methods: A MTT reduction assay was performed to evaluate thecytotoxicity of S-863d and S-863g on NHEK cells. NHEK cells were treatedwith S-863d or S-863g and incubated for 48 hours. After 48 hours, theNHEK cells were incubated with MTT (tetrazolium salt) reduced in blueformazan crystals by succinate dehydrogenase (mitochondrial enzyme). Thetransformation was proportional to enzyme activity. After celldissociation and formazan crystal solubilization using DMSO, the opticaldensity (OD) of the extracts at 40 nm was recorded. The OD was measuredwith a spectrometer (VERSAmax, Molecular Devices) and was used toestimate the proportion of living cells and their metabolic activity.

Viability was measured according to the following formula: viability(%)=(OD_(sample)/OD_(control))×100.

The effect of S-863d and S-863g on cytotoxicity are found in Tables 6and Table 7.

TABLE 6 Effect of compound S-863d on the viability of keratinocytesafter 48 hours of incubation S-863d Unit: % Control 1.83E−04 0.001 0.0030.012 0.047 0.188 0.750 3 Viability 96 88 94 89 83 81 94 93 51 38 107105 97 91 82 87 101 100 58 47 102 102 101 102 88 90 100 98 58 49 Mean100 97 94 85 86 98 97 56 45 Sem 3 2 4 2 3 2 2 2 3 Morphological + + + ++/− +/−, * −, * −, op Observations Codification +: normal population;+/−: growth reduction; −: toxicity; 0: cell mortality g: grains ofcompound; op: opacity of the compound; * morphological modification; ag:agglutinated cells

TABLE 7 Effect of compound S-863 g on the viability of keratinocytesafter 48 hours of incubation S-863 g Unit: % Control 1.83E−04 0.0010.003 0.012 0.047 0.188 0.750 3 Viability 102 94 100 102 100 0 1 0 5 17103 99 105 108 97 0 1 0 8 26 105 97 106 104 101 1 1 0 8 24 Mean 100 104105 99 0 1 0 7 23 Sem  2 2 2 1 0 0 0 1 3 Morphological + + + −, * −, *−, *, g 0, g op Observations Codification +: normal population; +/−:growth reduction; −: toxicity; 0: cell mortality g: grains of compound;op: opacity of the compound; * morphological modification; ag:agglutinated cells

Example 8. Effect of Composition Containing Rose Oil, a Humectant, andCBD on Migration of Human Keratinocyte Stem Cells

The effect of S-863d and S-863g on wound healing in keratinocytes wasevaluated. The migration of human keratinocyte stem cells (KSC) wasevaluated by measuring wound recovery using imaging on a system wherebya “wound gap” was created by scratching.

Materials: Human keratinocyte cells (KSC) were used at the third passageand cultured at 37° C. in the presence of 5% CO2. The NHEK cells weregrown in keratinocyte serum free media supplemented with gentamycin (25μg/mL), pituitary extract (PE) (25 μg/mL), and epidermal growth factor(EGF) (0.25 ng/ml). S-863d contained 3% phospholipids, 54% glycerin, 10%caprylic/capric triglyceride, 1% cannabidiol, 2% AlpineRoseActive™, 1%glycoin, 0.1% tocopherol, and water (ad 100%). The particle size (zAve)of S-863d was 90±50 nm, and the pH of S-863d was between 4.5 and 7.5.The total germ count of S-863d was <100 CFU/g. S-863d was stored at 4°C. in a dark space in a closed container. S-863g (negative control)contained 1% CBD in DMSO. S-863d was evaluated at 0.004%, 0.02%, and0.1%. S-863g was evaluated at 0.00044%, 0.0013%, and 0.004%.

Methods: The KSCs were seeded in 24-well plates (previously coated witha collagen I solution) and cultured in culture medium for 24 hours. Themedium was then replaced by assay medium and an artificial “wound gap”was generated by scratching the cell monolayers. The KSCs were labeledwith calcien-AM. After 30 minutes of incubation (TO), the medium wasreplaced by assay medium containing or not (control condition) the testcompounds or the reference compound (e.g. epidermal growth factor (EGF)at 10 ng/mL) and the cells were further incubated for 24 hours. Thelabeling with calcein-AM was renewed before the final timepoint. Allexperimental conditions were performed in triplicate. Cell migrationinto the migration zone was observed after 0 (TO) and 24 hours ofincubation using a high-resolution imaging system INCell Analyzer™ 2200(GE Healthcare) automated microscope and the artificial wound area wasanalyzed using ImageJ software. One picture was taken per well(objective lens ×4). The artificial wound area was measured after 24hours of incubation and compared to the area measured at TO in order tovisualize and quantify the wound recovery. The effect of compounds oncell migration was compared to the untreated control.

The migration area (percentage of wound recovery) was calculated usingthe following formula:

${{Wound}\mspace{14mu}{recovery}\mspace{14mu}(\%)} = {100 - {\left( {\frac{{Wound}\mspace{14mu}{Area}}{{Initial}\mspace{14mu}{Wound}\mspace{14mu}{Area}} \times 100} \right).}}$

In the control condition, KSC migration was moderate with a mean woundrecovery of 40% after 24 hours of incubation. The reference compound,EGF, induced a marked stimulation on KSC migration. Indeed, the woundgap recovery reached 73% after 24 hours of incubation, validating theassay. Compound S-863d, tested at 0.004%, 0.02%, and 0.1%, stimulatedthe migration of keratinocytes and reached a maximum of about 201% ofthe control at a concentration of 0.02%.

Compound S-863g, tested at 0.00044% and 0.0013%, also stimulated woundrecovery at a slightly lower level than S-863d (maximum 176% of thecontrol—although the tested concentrations were lower). Table 10 showsthe effect of compounds S-863d and S-863g on the migration of KSCS after24 hours of incubation. The underlined images from Table 8 are shown inFIG. 1. FIG. 1 shows representative images of the effect of compoundsS-863d and S-863g on the migration of KSCs.

TABLE 8 Effect of compounds S-863 d and S-863 g on the migration ofkeratinocyte stem cells after 24 hours of incubation T0 24 Hours InitialWound Treatment Wound Area Wound area Recovery Mean Sem % sem Testcompound Concentration Image (mm²) (mm²) (%) (%) (%²) Control (%) p⁽¹⁾Control — T-1 2.56 1.51 41 40 1 100 3 — T-2 2.26 1.32 42 T-3 2.39 1.4937 EGF 10 ng/ml R-1 2.35 0.46 80 73 5 183 12 ** R-2 1.99 0.50 75 R-32.11 0.76 64 S-863 d 0.004% 43-1 2.35 0.75 68 63 3 157 8 ** 43-2 1.750.75 57 43-3 1.88 0.70 63 0.02% 42-1 2.48 0.58 77 80 3 201 9 *** 42-21.85 0.42 77 42-3 2.45 0.31 87 0.1% 41-1 2.41 0.71 71 80 5 200 12 **41-2 2.23 0.27 88 41-3 1.88 0.35 81 S-863 g 0.00044% 73-1 1.72 0.77 5566 8 164 21 * 73-2 1.43 0.25 82 73-3 2.28 0.92 60 0.0013% 72-1 1.93 0.1791 71 11 176 26 * 72-2 1.87 0.71 62 72-3 2.51 1.04 58 0.004% 71-1 2.301.16 49 50 5 124 12 ns 71-2 1.79 1.05 41 71-3 2.17 0.90 58 ⁽¹⁾Thresholdfor statistical significance; ns: >0.05 Not significant; * 0.01 to 0.05Significant; ** 0.001 to 0.01 Very significant; *** <0.001, Extremelysignificant

Example 9. Effect of Composition Containing Rose Oil, a Humectant, andCBD on IL-8 and Prostaglandin E2 Release by a Keratinocyte Cell Line

The effect of S-863d and S-863g on inflammation in keratinocytes wasevaluated by measuring phorbol myristate acetate (PMA)-inducedinterleukin-8 (IL-8) and prostaglandin E2 (PGE₂) release from aNCTC-2544 keratinocyte cell line by enzyme-linked immunosorbent assay(ELISA).

Materials: A NCTC-2544 human keratinocyte cell line (NCTC-2544 cells)was cultured at 37° C. in the presence of 5% CO2. The NCTC-2544 cellswere grown in Dulbecco's Modified Eagle Medium (DMEM) supplemented withL-glutamine (2 mM), penicillin (50 U/mL), Streptomycin (50 μg/mL), andfetal calf serum (FCS) (10%). S-863d contained 3% phospholipids, 54%glycerin, 10% caprylic/capric triglyceride, 1% cannabidiol, 2%AlpineRoseActive™, 1% glycoin, 0.1% tocopherol, and water (ad 100%). Theparticle size (zAve) of S-863d was 90±50 nm, and the pH of S-863d wasbetween 4.5 and 7.5. The total germ count of S-863d was <100 CFU/g.S-863d was stored at 4° C. in a dark space in a closed container. S-863g(negative control) contained 1% CBD in DMSO. S-863d was evaluated at0.004%, 0.02%, and 0.1%. S-863g was evaluated at 0.00044%, 0.0013%, and0.004%.

Methods: The keratinocytes were seeded in 96-well plates and culturedfor 24 hours in culture medium. The medium was then replaced by culturemedium containing or not (control) the test compounds or the referencecompound (dexamethasone at 10⁻⁷ M for IL-8 assay and indomethacin at10⁻⁶ M for PGE₂ assay) and the cells were pre-incubated for 24 hours.After pre-incubation, the medium was replaced by culture mediumcontaining or not (control) the test compounds or the referencecompounds and the inflammatory inducer phorbol myristate acetate (PMA)at 0.1 μg/mL was added. The cells were further incubated for 24 hours. Acontrol without inducer was performed in parallel (non-stimulatedcontrol condition). All experimental conditions were performed intriplicate. IL-8 and PGE2 released in the culture supernatants weremeasured by ELISA.

Inhibition of IL-8 and PMA-induced PGE₂ release was measured using thefollowing formula:

${{Relative}\mspace{14mu}{Inhibition}\mspace{14mu}(\%)} = {\left( \frac{{Mean}_{{stimulated}\mspace{14mu}{control}} - {Value}}{{Mean}_{{stimulated}\mspace{14mu}{control}} - {Mean}_{{non}\text{-}{stimulated}\mspace{14mu}{control}}} \right) \times 100.}$

Results: A treatment of NCTC-2544 keratinocytes with PMA at 0.1 μg/mLstrongly increased IL-8 release (˜120000 pg/mL) while basal IL-8 releasewas limited in the non-stimulated control condition (˜350 pg/mL). Thereference compound, dexamethasone, tested at 10⁻⁷ M, strongly inhibitedPMA-induced IL-8 release (18% of the stimulated control), validating theassay. Under the experimental conditions of the assay, compounds S-863dand S-863g did not have any significant effect on PMA-induced IL-8release in the NCTC-2544 cells, as shown in Table 9.

Under non-stimulated control conditions, no basal PGE₂ release wasdetected in NCTC-2544 keratinocytes and the treatment with PMA at 0.1μg/mL resulted in a very strong release of PGE₂ (˜220000 pg/mL). Thereference compound indomethacin, tested at 10⁻⁶M, completely inhibitedthis effect, validating the assay. Under the experimental conditions ofthis study, compound S-863d presented a trend for aconcentration-dependent inhibitory effect on PMA-induced PGE2 release,reaching 59% of the control when tested at 0.1%. Compound S-863g did notdisplay any clear effect on PMA-induced PGE2 release in the NCTC-2544cells. Table 10 shows the results of this study.

The results of this study showed that compound S-863d exhibitedanti-inflammatory properties by inhibiting PGE₂ release by keratinocytesstimulated with PMA. This formulation also had a strong stimulatingeffect on keratinocyte migration suggesting that it has interestingwound healing properties. In contrast, S-863g, tested as a negativecontrol, had no anti-inflammatory properties and its stimulating effecton keratinocyte migration was less marked than compound S-863d.

TABLE 9 Effect of compounds S-863 d and S-863 g on PMA-induced IL-8release by NCTC-2544 keratinocytes Basic data IL-8 (pg/ml) Normalizeddata dilution % % Treatment factor Mean sem Stimulated sem Relative semTest compound Concentration adjusted (pg/ml) (pg/ml) control (%) p⁽¹⁾inhibition (%) p⁽¹⁾ Non-stimulated —   363 349 8 0 0 *** 100 0 ***control^(#)   336   347 Stimulated Control — 109321 120084 7707 100 6 —0 6 — conditions: 115910 PMA - 0.1 135021 μg/ml Dexamethasone 10⁻⁷ M 18117 22112 2097 18 2 *** 82 2 ***  23002  25217 S-863 d 0.004% 116481147172 15527 123 13 ns −23 13 ns 158416 166618 0.02% 116531 134025 12866112 11 ns −12 11 ns 159116 126429 0.1% 132589 137457 4867 114 4 nc −15 4nc 142324  185512⁽²⁾ S-863g 0.00044%  92046 102451 5204 85 4 ns 15 4 ns107904 107401 0.0013%  93461 100505 6388 84 5 ns 16 5 ns 113257  94796102302 105124 6150 88 5 ns 12 5 ns 0.004% 116902  96167 ⁽¹⁾Threshold forstatistical significance ns: >0.05, Not significant * 0.01 to 0.05,Significant ** 0.001 to 0.01, Very significant *** <0.001, Extremelysignificant nc: Not calculable ⁽²⁾Rejected Data ^(#)Non-diluted samples

TABLE 10 Effect of compounds S-863 d and S-863 g on PMA-induced PGE₂release by NCTC-2544 keratinocytes Basic data PGE₂ (pg/ml) Normalizeddata dilution % % Treatment factor Mean sem Stimulated sem Relative semTest compound Concentration adjusted (pg/ml) (pg/ml) control (%) p⁽¹⁾inhibition (%) p⁽¹⁾ Non-stimulated — <39 <39 0 <0 0 *** 100 0 ***control^(#) <39 <39 Stimulated Control — 185876 219105 19936 100 9 — 0 9— conditions: 216634 PMA - 0.1 254805 μg/ml Indomethacin^(#) 10⁻⁶ M <39<39 0 <0 0 *** >100 0 *** <39 <39 S-863 d 0.004% 171587 210547 21657 9610 ns 4 10 ns 213634 246419 0.02% 162514 181874 11054 83 5 ns 17 5 ns182307 200800 0.1% 115120 130333 11520 59 5 * 41 5 * 122952 152926S-863g 0.00044% 195605 180465 33572 82 15 ns 18 15 ns 116243 2295450.0013% 178945 202710 12182 93 6 ns 7 6 ns 209944 219241 0.004% 147522173636 18019 79 8 ns 21 8 ns 165184 208201 ⁽¹⁾Threshold for statisticalsignificance ns: >0.05, Not significant * 0.01 to 0.05, Significant **0.001 to 0.01, Very significant *** <0.001, Extremely significant <or >: Inferior or superior to the detection limit <39.1 or >2500 pg/mlfor non-diluted samples <15640 or >1000000 pg/ml for diluted samples at1/400 In case of values < or > to detection limits, ensuing calculationsare extrapolated. ^(#)Non-diluted samples

Numbered Embodiments of the Disclosure

Notwithstanding the appended claims, the disclosure sets forth thefollowing numbered embodiments:

1. A topical skin care composition comprising:

(i) rose oil;

(ii) cannabidiol (CBD), and

(iii) a humectant,

wherein the composition is delivered to skin by a cosmetic vehicle.

2. The topical skin care composition of embodiment 1, comprising up toabout 5% rose oil and up to about 2% CBD.

3. The topical skin care composition of embodiments 1 and 2, comprisingup to about 2% of a humectant.

4. The topical skin care composition of embodiment 3, wherein thehumectant is selected from the group consisting of Aloe vera extract,glyceryl glucoside, and hyaluronic acid.

5. The topical skin care composition of embodiment 4, wherein thehumectant is hyaluronic acid.

6. The topical skin care composition of embodiment 4, wherein thehumectant is glyceryl glucoside.

7. The topical skin care composition of embodiment 1, wherein the roseoil is an extract of Rhododendron ferrugineum.

8. The topical skin care composition of embodiment 7, wherein theextract comprises stem cells.

9. The topical skin care composition of embodiment 1, wherein the roseoil is an extract of Rosa damascena.

10. The topical skin care composition of embodiment 1, wherein thecosmetic vehicle is selected from the group consisting of liposome,nanosome, oil-in-water emulsion, and water-in-oil emulsion.

11. The topical skin care composition of embodiment 1, wherein thecosmetic vehicle is a nanosome.

12. The topical skin care composition of embodiment 11, wherein thenanosome has an average particle size of 90 nm.

13. The topical skin care composition of embodiment 1, wherein thecosmetic vehicle is an oil-in-water emulsion.

14. The topical skin care composition of embodiment 1, wherein thecosmetic vehicle comprises up to about 60% glycerin, up to about 15%caprylic/capric triglycerides, and up to about 3% phospholipids.

15. A method of applying the topical skin care composition of embodiment1 to skin, comprising topically applying the topical skin carecomposition of embodiment 1.

16. The method of embodiment 15, wherein the composition is applied to aface.

17. The method of embodiment 15, wherein the composition is applied to awrinkle.

18. The method of embodiment 15, wherein the composition is applied to afine line.

19. A method of reducing acne comprising applying the topical skin carecomposition of embodiment 1 to the skin.

20. The topical skin care composition of embodiment 1, wherein thecomposition is incorporated into a product selected from the groupconsisting of an eye cream, a serum, a face mask, and a lotion.

21. The topical skin care composition of embodiment 1, wherein thecomposition further comprises tocopherol.

22. The topical skin care composition of embodiment 1, comprising 2% v/vrose oil, 1% w/v CBD, 54% v/v glycerin, 1% v/v hyaluronic acid, 0.1% v/vtocopherol, 3% v/v phospholipids, and 10% v/v caprylic/caprictriglycerides, wherein the rose oil is an extract from Rhododendronferrugineum.23. The topical skin care composition of embodiment 1, comprising 2% v/vrose oil, 1% v/v CBD, 54% v/v glycerin, 1% v/v hyaluronic acid, 0.1% v/vtocopherol, 3% v/v phospholipids, and 10% v/v caprylic/caprictriglycerides, wherein the rose oil is an extract from Rhododendronferrugineum.24. The topical skin care composition of embodiment 1, comprising 2% v/vrose oil, 1% w/v CBD, 54% v/v glycerin, 1% v/v hyaluronic acid, 3% v/vphospholipids, and 10% v/v caprylic/capric triglycerides, wherein therose oil is an extract from Rhododendron ferrugineum.25. The topical skin care composition of embodiment 1, comprising 2% v/vrose oil, 1% v/v CBD, 54% v/v glycerin, 1% v/v hyaluronic acid, 3% v/vphospholipids, and 10% v/v caprylic/capric triglycerides, wherein therose oil is an extract from Rhododendron ferrugineum.

INCORPORATION BY REFERENCE

All references, articles, publications, patents, patent publications,and patent applications cited herein are incorporated by reference intheir entireties for all purposes. However, mention of any reference,article, publication, patent, patent publication, and patent applicationcited herein is not, and should not be taken as, an acknowledgment orany form of suggestion that they constitute valid prior art or form partof the common general knowledge in any country in the world.Furthermore, International Application Publication No. WO 2008/010241A1,published Jan. 24, 2008, entitled: A Liposomal Complex of SodiumCarboxmethyl Beta-Glucan, is hereby incorporated by reference.

What is claimed is:
 1. A topical skin care composition comprising: (i)from about 0.5% w/w to about 5.0% w/w rose oil; (ii) from about 1.0% w/wto about 5.0% w/w cannabidiol (CBD), and (iii) glyceryl glucoside,wherein the composition is formulated for delivery to skin by a cosmeticvehicle.
 2. The topical skin care composition of claim 1, comprisingabout 2% w/w rose oil.
 3. The topical skin care composition of claim 1,comprising up to about 1% w/w of glyceryl glucoside.
 4. The topical skincare composition of claim 1, further comprising hyaluronic acid.
 5. Thetopical skin care composition of claim 1, wherein the rose oil is anextract of Rhododendron ferrugineum.
 6. The topical skin carecomposition of claim 5, wherein the extract comprises stem cells.
 7. Thetopical skin care composition of claim 1, wherein the rose oil is anextract of Rosa damascena.
 8. The topical skin care composition of claim1, wherein the cosmetic vehicle is selected from the group consisting ofliposome, nanosome, oil-in-water emulsion, and water-in-oil emulsion. 9.The topical skin care composition of claim 1, wherein the cosmeticvehicle is a nanosome.
 10. The topical skin care composition of claim 9,wherein the nanosome has an average particle size of 90 nm.
 11. Thetopical skin care composition of claim 1, wherein the cosmetic vehicleis an oil-in-water emulsion.
 12. The topical skin care composition ofclaim 1, wherein the cosmetic vehicle comprises up to about 60% v/vglycerin, up to about 15% v/v caprylic/capric triglycerides, and up toabout 3% v/v phospholipids.
 13. The topical skin care composition ofclaim 1, comprising tocopherol.
 14. A method of applying the topicalskin care composition of claim 1 to skin, comprising topically applyingthe topical skin care composition of claim
 1. 15. The method of claim14, wherein the composition is applied to a face.
 16. The method ofclaim 14, wherein the composition is applied to a wrinkle.
 17. Themethod of claim 14, wherein the composition is applied to a fine line.18. A method of reducing acne comprising applying the topical skin carecomposition of claim 1 to the skin.
 19. The topical skin carecomposition of claim 1, wherein the composition is incorporated into aproduct selected from the group consisting of an eye cream, a serum, aface mask, and a lotion.
 20. The topical skin care composition of claim1, comprising 2% w/w rose oil, 1% w/w CBD, 54% w/w glycerin, 1% w/wglyceryl glucoside acid, 0.1% w/w tocopherol, 3% w/w phospholipids, and10% w/w caprylic/capric triglycerides, wherein the rose oil is anextract from Rhododendron ferrugineum.
 21. The topical skin carecomposition of claim 1, comprising 2% w/w rose oil, 1% w/w CBD, 54% w/wglycerin, 1% w/w glyceryl glucoside acid, 3% w/w phospholipids, and 10%w/w caprylic/capric triglycerides, wherein the rose oil is an extractfrom Rhododendron ferrugineum.
 22. A topical skin care compositioncomprising: (i) about 2.0% w/w rose oil; (ii) about 1.0% w/w cannabidiol(CBD), and (iii) about 1% glyceryl glucoside, wherein the composition isformulated for delivery to skin by a cosmetic vehicle.
 23. The topicalskin care composition of claim 1, comprising about 1 w/w CBD.